WO2020110646A1 - Chip for detecting material derived from living body, apparatus for detecting material derived from living body, and system for detecting material derived from living body - Google Patents

Chip for detecting material derived from living body, apparatus for detecting material derived from living body, and system for detecting material derived from living body Download PDF

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Publication number
WO2020110646A1
WO2020110646A1 PCT/JP2019/043641 JP2019043641W WO2020110646A1 WO 2020110646 A1 WO2020110646 A1 WO 2020110646A1 JP 2019043641 W JP2019043641 W JP 2019043641W WO 2020110646 A1 WO2020110646 A1 WO 2020110646A1
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Prior art keywords
chip
substance detection
holding surface
biogenic
detection chip
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PCT/JP2019/043641
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French (fr)
Japanese (ja)
Inventor
佳明 桝田
慎太郎 中食
幸香 大久保
山崎　知洋
Original Assignee
ソニーセミコンダクタソリューションズ株式会社
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Priority to US17/287,591 priority Critical patent/US20210318247A1/en
Priority to EP19890530.9A priority patent/EP3889584A4/en
Priority to CN201980077118.5A priority patent/CN113167730A/en
Publication of WO2020110646A1 publication Critical patent/WO2020110646A1/en

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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
    • G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
    • G01N21/64—Fluorescence; Phosphorescence
    • G01N21/6486—Measuring fluorescence of biological material, e.g. DNA, RNA, cells
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
    • G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
    • G01N21/64—Fluorescence; Phosphorescence
    • G01N21/645—Specially adapted constructive features of fluorimeters
    • G01N21/6452—Individual samples arranged in a regular 2D-array, e.g. multiwell plates
    • G01N21/6454—Individual samples arranged in a regular 2D-array, e.g. multiwell plates using an integrated detector array
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/502715—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01J—MEASUREMENT OF INTENSITY, VELOCITY, SPECTRAL CONTENT, POLARISATION, PHASE OR PULSE CHARACTERISTICS OF INFRARED, VISIBLE OR ULTRAVIOLET LIGHT; COLORIMETRY; RADIATION PYROMETRY
    • G01J3/00—Spectrometry; Spectrophotometry; Monochromators; Measuring colours
    • G01J3/02—Details
    • G01J3/0205—Optical elements not provided otherwise, e.g. optical manifolds, diffusers, windows
    • G01J3/0208—Optical elements not provided otherwise, e.g. optical manifolds, diffusers, windows using focussing or collimating elements, e.g. lenses or mirrors; performing aberration correction
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01J—MEASUREMENT OF INTENSITY, VELOCITY, SPECTRAL CONTENT, POLARISATION, PHASE OR PULSE CHARACTERISTICS OF INFRARED, VISIBLE OR ULTRAVIOLET LIGHT; COLORIMETRY; RADIATION PYROMETRY
    • G01J3/00—Spectrometry; Spectrophotometry; Monochromators; Measuring colours
    • G01J3/28—Investigating the spectrum
    • G01J3/2803—Investigating the spectrum using photoelectric array detector
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/25—Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands
    • G01N21/27—Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands using photo-electric detection ; circuits for computing concentration
    • G01N21/272—Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands using photo-electric detection ; circuits for computing concentration for following a reaction, e.g. for determining photometrically a reaction rate (photometric cinetic analysis)
    • H—ELECTRICITY
    • H01—ELECTRIC ELEMENTS
    • H01L—SEMICONDUCTOR DEVICES NOT COVERED BY CLASS H10
    • H01L31/00—Semiconductor devices sensitive to infrared radiation, light, electromagnetic radiation of shorter wavelength or corpuscular radiation and specially adapted either for the conversion of the energy of such radiation into electrical energy or for the control of electrical energy by such radiation; Processes or apparatus specially adapted for the manufacture or treatment thereof or of parts thereof; Details thereof
    • H01L31/02—Details
    • H01L31/0216—Coatings
    • H01L31/02161—Coatings for devices characterised by at least one potential jump barrier or surface barrier
    • H01L31/02162—Coatings for devices characterised by at least one potential jump barrier or surface barrier for filtering or shielding light, e.g. multicolour filters for photodetectors
    • H01L31/02164—Coatings for devices characterised by at least one potential jump barrier or surface barrier for filtering or shielding light, e.g. multicolour filters for photodetectors for shielding light, e.g. light blocking layers, cold shields for infrared detectors
    • H—ELECTRICITY
    • H01—ELECTRIC ELEMENTS
    • H01L—SEMICONDUCTOR DEVICES NOT COVERED BY CLASS H10
    • H01L31/00—Semiconductor devices sensitive to infrared radiation, light, electromagnetic radiation of shorter wavelength or corpuscular radiation and specially adapted either for the conversion of the energy of such radiation into electrical energy or for the control of electrical energy by such radiation; Processes or apparatus specially adapted for the manufacture or treatment thereof or of parts thereof; Details thereof
    • H01L31/02—Details
    • H01L31/0232—Optical elements or arrangements associated with the device
    • H01L31/02325—Optical elements or arrangements associated with the device the optical elements not being integrated nor being directly associated with the device
    • H—ELECTRICITY
    • H01—ELECTRIC ELEMENTS
    • H01L—SEMICONDUCTOR DEVICES NOT COVERED BY CLASS H10
    • H01L31/00—Semiconductor devices sensitive to infrared radiation, light, electromagnetic radiation of shorter wavelength or corpuscular radiation and specially adapted either for the conversion of the energy of such radiation into electrical energy or for the control of electrical energy by such radiation; Processes or apparatus specially adapted for the manufacture or treatment thereof or of parts thereof; Details thereof
    • H01L31/02—Details
    • H01L31/0232—Optical elements or arrangements associated with the device
    • H01L31/02327—Optical elements or arrangements associated with the device the optical elements being integrated or being directly associated to the device, e.g. back reflectors
    • H—ELECTRICITY
    • H01—ELECTRIC ELEMENTS
    • H01L—SEMICONDUCTOR DEVICES NOT COVERED BY CLASS H10
    • H01L31/00—Semiconductor devices sensitive to infrared radiation, light, electromagnetic radiation of shorter wavelength or corpuscular radiation and specially adapted either for the conversion of the energy of such radiation into electrical energy or for the control of electrical energy by such radiation; Processes or apparatus specially adapted for the manufacture or treatment thereof or of parts thereof; Details thereof
    • H01L31/08—Semiconductor devices sensitive to infrared radiation, light, electromagnetic radiation of shorter wavelength or corpuscular radiation and specially adapted either for the conversion of the energy of such radiation into electrical energy or for the control of electrical energy by such radiation; Processes or apparatus specially adapted for the manufacture or treatment thereof or of parts thereof; Details thereof in which radiation controls flow of current through the device, e.g. photoresistors
    • H01L31/10—Semiconductor devices sensitive to infrared radiation, light, electromagnetic radiation of shorter wavelength or corpuscular radiation and specially adapted either for the conversion of the energy of such radiation into electrical energy or for the control of electrical energy by such radiation; Processes or apparatus specially adapted for the manufacture or treatment thereof or of parts thereof; Details thereof in which radiation controls flow of current through the device, e.g. photoresistors characterised by at least one potential-jump barrier or surface barrier, e.g. phototransistors
    • H01L31/101—Devices sensitive to infrared, visible or ultraviolet radiation
    • H01L31/102—Devices sensitive to infrared, visible or ultraviolet radiation characterised by only one potential barrier or surface barrier
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/14—Process control and prevention of errors
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/06—Auxiliary integrated devices, integrated components
    • B01L2300/0627—Sensor or part of a sensor is integrated
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2201/00—Features of devices classified in G01N21/00
    • G01N2201/06—Illumination; Optics
    • G01N2201/064—Stray light conditioning

Definitions

  • the present technology relates to a biogenic substance detection chip, a biogenic substance detection device, and a biogenic substance detection system.
  • Optical detection including at least a third substrate provided with a plurality of light irradiation means and a fourth substrate provided with a plurality of light detection means positioned corresponding to the positions of the respective wells A device is disclosed. This optical detection device can measure various reactions progressing in each well.
  • Patent Document 2 discloses a chemical sensor including a substrate on which a photodetection portion is formed, and a plasmon absorption layer having a metal nanostructure that causes plasmon absorption and is stacked on the substrate. There is. With this chemical sensor, it is possible to detect the luminescence due to the bond between the probe material and the target material fixed on the sensor.
  • the main purpose of the present technology is to provide a biogenic substance detection chip with high detection accuracy.
  • the pixel includes at least a holding surface that holds a biological substance, and a photoelectric conversion unit that is provided below the holding surface and that is provided on a semiconductor substrate.
  • a biogenic substance detection chip in which a color mixture suppressing unit is provided between the pixels.
  • the pixel and the color mixing suppression unit may have different conductivity types.
  • the pixel may be an N-type region and the color mixture suppressing unit may be a P-type region.
  • the pixel may be a P-type region and the color mixture suppressing portion may be an N-type region.
  • each of the plurality of pixels has a photoelectric conversion region, and a trench can be provided between the photoelectric conversion regions.
  • at least one selected from an oxide film and a metal may be included inside the trench.
  • a recess may be provided on the holding surface above the photoelectric conversion unit.
  • the holding surface may be provided on a film formed on the semiconductor substrate.
  • the film may have a first refractive index
  • the semiconductor substrate may have a second refractive index different from the first refractive index.
  • the film may be one or more films selected from an inorganic film and an organic film.
  • the biogenic substance detection chip according to the present technology may include a light-shielding film provided above the adjacent pixels.
  • the space between the light shielding films may be formed to have one or more shapes selected from a circle, an ellipse, and a polygon having an R shape in a top view.
  • the holding surface may be provided on an on-chip lens (OCL) provided on the semiconductor substrate.
  • OCL on-chip lens
  • the holding surface may be provided on a flattening film formed on the on-chip lens (OCL).
  • the biogenic substance that can be detected by the biogenic substance detection chip according to the present technology is selected from nucleic acids, proteins, cells, microorganisms, chromosomes, liposomes, mitochondria, organelles (organelles), and complexes thereof.
  • One or more biological materials can be mentioned.
  • the pixel includes at least a holding surface for holding a biological substance, and a photoelectric conversion unit provided below the holding surface, A color mixing suppression part is provided between the pixels, a chip for detecting a biological substance, An analysis unit that analyzes electrical information acquired by the biological substance detection chip, An apparatus for detecting a substance derived from a living body, comprising:
  • the present technology further includes a plurality of pixels,
  • the pixel includes at least a holding surface for holding a biological substance, and a photoelectric conversion unit provided below the holding surface, A color mixing suppression part is provided between the pixels, a chip for detecting a biological substance, An analysis device that analyzes the electrical information acquired by the biogenic substance detection chip,
  • a biological substance detection system comprising:
  • living material shall broadly include nucleic acids, proteins, cells, microorganisms, chromosomes, liposomes, mitochondria, organelles (organelles), complexes thereof, and the like.
  • Cells include animal cells (such as blood cells) and plant cells.
  • Microorganisms include bacteria such as Escherichia coli, viruses such as tobacco mosaic virus, fungi such as yeast.
  • FIG. 2 is a schematic conceptual diagram schematically showing the interaction of the biogenic substance S that can be detected by the biogenic substance detection chip 1, the biogenic substance detection device 2, and the biogenic substance detection system 3 according to the present technology.
  • FIG. 2 is a schematic conceptual diagram schematically showing the interaction of the biogenic substance S that can be detected by the biogenic substance detection chip 1, the biogenic substance detection device 2, and the biogenic substance detection system 3 according to the present technology.
  • FIG. 2 is a schematic conceptual diagram schematically showing the interaction of the biogenic substance S that can be detected by the biogenic substance detection chip 1, the biogenic substance detection device 2, and the biogenic substance detection system 3 according to the present technology. ..
  • A is a schematic end view schematically showing a second embodiment of the biogenic substance detection chip 1 according to the present technology
  • B is a schematic cross-sectional view schematically showing a modified example of the second embodiment.
  • .. It is a schematic cross section which shows typically 3rd Embodiment of the chip
  • FIG. 25 is a schematic cross-sectional view taken along the line AA of FIG. 24 in which the internal structure is omitted. It is a block diagram which shows the concept of the biological substance detection apparatus 2 which concerns on this technique. It is a block diagram which shows the concept of the biological substance detection system 3 which concerns on this technique.
  • the biogenic substance detection chip 1, the biogenic substance detection device 2, and the biogenic substance detection system 3 according to the present technology include (1) detection of the biogenic substance S itself, and (2) interaction of the biogenic substance S. And (3) screening of other substances (for example, medicinal components) using the biogenic substance S. In addition, each detection is performed on the holding surface 111 of the biogenic substance detection chip 1 described later.
  • Detection of the body-derived substance S itself
  • biological substances such as red blood cells, white blood cells, platelets, cytokines, hormonal substances, sugars, lipids and proteins contained in body fluids such as blood, urine, feces and saliva
  • the present technology can be used for detecting microorganisms such as bacteria, fungi, and viruses contained in water; genes in cells and microorganisms.
  • the presence of the substance to be detected can be detected by the presence or absence of the desired light detection after dyeing with a dye that specifically acts on the substance to be detected or the substance not to be detected.
  • the detected results can be used for diagnosis of diseases, internal environment diagnosis, water quality test and the like.
  • the present technology can be used for detection of interaction such as protein interaction, nucleic acid hybridization, and binding between cytokine or hormone substance and receptor.
  • detection of interaction such as protein interaction, nucleic acid hybridization, and binding between cytokine or hormone substance and receptor.
  • a specific detection example will be described with reference to FIGS.
  • a biological substance S1 such as a protein or a receptor (or a model imitating a receptor) is immobilized on the holding surface 111 (see A in FIG. 1).
  • a substance in which a dye such as fluorescence F1 to F3 is immobilized is added to the biogenic substances S2 to S4 for confirming the interaction with (see B in FIG. 1).
  • the biological substances S3 and S4 that have not interacted with each other are washed (see C in FIG. 1), and the fluorescence F1 is detected from the holding surface 111 (see D in FIG. 1), whereby the biological substance S1 and the biological substance The interaction with the derived substance S2 can be detected.
  • a biogenic substance S1 such as cells is immobilized on the holding surface 111, and the transporter t of the biogenic substance S1 (for example, a transporter in a cell membrane). It is possible to detect the illuminant F1 that is taken in through.
  • a probe S5 made of DNA, RNA or the like is immobilized on the holding surface 111 (see A in FIG. 2), and a sample containing DNAs S6 and S7 that can be targets and Add Calculator I (see B in Figure 2). Then, when DNA S6 having a sequence complementary to probe S5 is contained in the sample, a hybridization reaction occurs. By washing the DNAS7 that has not been hybridized (see C in FIG. 2) and detecting the light from the intercalator I from the holding surface 111 (see D in FIG. 2), the probe S5 and the target DNAS6 are detected. Hybridization can be detected.
  • the biogenic substance S8 is fixed on the holding surface 111 (see A in FIG. 3), and interacts with this to form a new substance S10, the biogenic substance S9. Is added (see B in FIG. 3).
  • a dye such as fluorescent F4 that specifically binds to the substance S10 is added (see C in FIG. 3), and the fluorescent F4 is detected from the holding surface 111 (see D in FIG. 3) to obtain the biologically derived substance S8.
  • the interaction with the biological substance S9 can be detected.
  • the receptor R1 (or a model imitating the receptor R1) is fixed to the holding surface 111 (see A in FIG. 4), and the operability of the receptor R1 is increased.
  • dyes such as fluorescent dyes F5 to F7 immobilized are added (see B in FIG. 4).
  • the substances d2 and d3 that have not bound to the receptor R1 are washed (see C in FIG. 4), and the fluorescence F5 is detected from the holding surface 111 (see D in FIG. 3) to activate the receptor R1. It is possible to screen the substance d1 which can be a drug.
  • the receptor R2 (or a model imitating the receptor R2) is immobilized on the holding surface 111 (see A in FIG. 5), and the receptor R2 has an antagonistic property.
  • the substance d4 for confirming is confirmed (see B in FIG. 5).
  • a ligand L1 that binds to the receptor R2 on which a dye such as fluorescent F8 is immobilized is added (see C in FIG. 5).
  • the substance d4 can be an antagonist of the receptor R2
  • the ligand L1 cannot bind to the receptor R2 because the receptor R2 and the substance d4 are already bound (see FIG. 5). (See C).
  • the receptor R3 (or a model imitating the receptor R3) is fixed to the holding surface 111 (see A in FIG. 6), and the receptor R3 A substance d5 for confirming antagonisticity is added (see B in FIG. 6).
  • a ligand L2 that binds to a receptor R3 having a dye such as fluorescent F9 immobilized thereon is added (see C in FIG. 6).
  • the substance d5 cannot be an antagonist of the receptor R3
  • the ligand L2 binds to the receptor R3 (see D in FIG. 6).
  • fluorescence F9 is detected from the holding surface 111 (see E in FIG. 6).
  • the substance d4 that can be an antagonist of the receptor R3 can be screened depending on whether or not the fluorescence F8 or the fluorescence F9 is detected from the holding surface 111.
  • the biogenic substance detection chip 1 includes a plurality of pixels 11.
  • the pixel 11 is provided on a holding surface 111 that holds the biogenic substance S, and is provided below the holding surface 111. At least the provided photoelectric conversion unit 112 is provided.
  • a color mixture suppression unit 13 is provided between each pixel 11.
  • FIG. 7 is a schematic cross-sectional view schematically showing a first embodiment of the biogenic substance detection chip 1 according to the present technology.
  • the biogenic substance detection chip 1 according to the first embodiment includes an effective pixel region 11E in which a plurality of pixels 11 are two-dimensionally arranged in a matrix.
  • Each pixel 11 includes at least a holding surface 111 that holds the biological substance S and a photoelectric conversion unit 112.
  • a photoelectric conversion element such as a photodiode can be freely used.
  • each pixel 11 may include a pixel circuit including a charge storage section, a plurality of transistors, a capacitive element, and the like.
  • an optical black pixel, a wiring region, or the like can be provided on the outside O of the effective pixel region 11E.
  • the holding surface 111 is not particularly limited as long as it can hold the biological substance S, and surface treatment can be freely used.
  • the holding surface 111 can be formed by applying a photosensitive silane coupling agent or the like that is hydrophilically modified by irradiation with ultraviolet rays and selectively irradiating the area where the biological substance S is desired to be retained with ultraviolet rays.
  • a biological substance S such as a nucleic acid having one end thereof biotinylated can be held by avidin-biotin bond.
  • a color mixture suppression unit 13 is provided between each pixel 11.
  • the pixels 11 and the color mixing suppression unit 13 have different conductivity types, thereby suppressing color mixing between the adjacent pixels 11.
  • the pixels 11 are N-type regions and the pixels 11 are P-type regions, or conversely, the pixels 11 are P-type regions and the pixels 11 are N-type regions. Color mixing between adjacent pixels 11 can be suppressed.
  • biogenic substance S is described for the sake of explanation, but the biogenic substance detection chip 1 according to the present technology does not include the biogenic substance S. ..
  • FIG. 8A is a schematic end view schematically showing a second embodiment of the biogenic substance detection chip 1 according to the present technology, and FIG. 8B shows the second embodiment. It is a schematic cross section which shows the modification of a form typically.
  • the biogenic substance detection chip 1 according to the second embodiment includes trenches 13T between the photoelectric conversion regions 112A, and the trenches 13T function as the color mixing suppression unit 13.
  • An oxide film 14 can be provided inside the trench 13T as shown in FIG. 8B.
  • Examples of the material of the oxide film 14 include materials having a negative fixed charge such as hafnium oxide (HfO 2 ), aluminum oxide (Al 2 O 3 ), and tantalum oxide (Ta 2 O 5 ). These oxide films may be provided as a single film or a plurality of films may be stacked. By providing the oxide film, dark current can be suppressed and erroneous determination can be suppressed.
  • an oxide film 14 and a metal 15 can be provided inside the trench 13T.
  • the metal 15 it is possible to enhance the light blocking effect, suppress color mixture to adjacent pixels, and suppress erroneous determination.
  • the oxide film 14 and the metal 15 inside the trench 13T it is possible to improve the color mixture suppressing effect between the adjacent pixels 11 while suppressing the dark current.
  • the oxide film described with reference to FIG. 8 can be used. That is, a silicon oxide film (SiO 2 film), a hafnium oxide film (HfO 2 film), an aluminum oxide film (Al 2 O 3 film), a tantalum oxide film (Ta 2 O 5 film), and the like can be given.
  • tungsten (W), aluminum (Al), copper (Cu), titanium (Ti) or the like can be used as the metal.
  • FIG. 10A is a schematic cross-sectional view schematically showing a fourth embodiment of the biogenic substance detection chip 1 according to the present technology.
  • the living body-derived substance detection chip 1 according to the fourth embodiment has a recess 111C on the holding surface 111 above the photoelectric conversion unit 112. By holding the biogenic substance S to be detected in the recess 111C, it is possible to prevent light from being scattered from the biogenic substance S.
  • the recess 111C can be provided with an oxide film 14 as shown in FIG. 10B.
  • the oxide film 14 it is possible to eliminate the color mixing path and improve the sensitivity.
  • the shape of the concave portion 111C is not particularly limited, and in addition to the substantially triangular shape in cross section as shown in FIGS. 10A and 10B, the substantially rectangular shape in cross section as shown in FIG. It can be designed in a substantially semicircular shape in cross section.
  • FIG. 11 is a schematic cross-sectional view schematically showing a fifth embodiment of the biogenic substance detection chip 1 according to the present technology.
  • the holding surface 111 is provided on the film 16 formed on the semiconductor substrate 12.
  • an inorganic film such as a tantalum oxide film (Ta 2 O 5 film), an organic film made of a resin material such as a styrene resin, an acrylic resin, a styrene-acryl copolymer resin, or a siloxane resin. it can.
  • the refractive index of the film 16 is preferably different from that of the semiconductor substrate 12.
  • the film 16 has a first refractive index and the semiconductor substrate 12 has a second refractive index different from the first refractive index. Since the refractive index of the film 16 and the refractive index of the semiconductor substrate 12 are different from each other, an angle-dependent optical design of the reflectance can be performed, and the lateral direction of the light from the biological substance S held on the holding surface 111 can be obtained. It is possible to prevent the light from being reflected to enter the semiconductor substrate 12, and as a result, it is possible to prevent color mixing between the pixels 11.
  • the film 16 can be included in the above-mentioned trench 13T as in the sixth to eighth embodiments shown in FIGS. 12 to 14. Further, the film 16 can be formed by laminating a plurality of films 16 or by laminating it with the oxide film 14 as in the eighth embodiment shown in FIG. 14, depending on the purpose.
  • FIG. 15 is a schematic cross-sectional view schematically showing a ninth embodiment of the biogenic substance detection chip 1 according to the present technology.
  • the biogenic substance detection chip 1 according to the ninth embodiment includes the light shielding film 17 provided above the adjacent pixels 11. Providing the light-shielding film 17 can further prevent color mixing between the pixels 11. Further, by providing the light shielding film 17, the liquid sample can be held on the holding surface 111, and the biological substance S can be held in the liquid.
  • the light-shielding film 17 can be freely selected as long as it is a film formed of a light-shielding material.
  • a metal film of tungsten (W), aluminum (Al), copper (Cu), titanium (Ti), etc., an optical black filter, etc. may be mentioned.
  • the form of the light-shielding film 17 is not particularly limited and can be freely designed according to the purpose. However, as shown in FIGS. 16A to 16C, a portion between the light-shielding films 17 (that is, the holding surface 111) is viewed from above. In, it is preferable to exhibit one or more shapes selected from a circle, an ellipse, and a polygon having R-shaped corners. As described above, by eliminating the corners in the top view between the light shielding films 17, it is possible to prevent uneven supply when the sample is supplied to the holding surface 111, cleaning defects when cleaning the holding surface 111, and the like. As a result, the detection accuracy can be further improved.
  • a method for preventing the uneven supply during the supply of the sample to the holding surface 111 and the cleaning defect during the cleaning of the holding surface 111 as another method, as in the tenth embodiment shown in FIG.
  • a method of providing the flattening film 19 using, for example, can also be adopted.
  • the light shielding film 17 can be embedded in the above-described trench 13T to form a light shielding wall from above the pixels 11 to the semiconductor substrate 12.
  • the light-shielding film 17 can be provided for each pixel 11 as shown in FIGS. 15 to 19, but it is also possible to provide the light-shielding film 17 for each of a plurality of pixels 11.
  • FIG. 20 is a schematic cross-sectional view schematically showing a thirteenth embodiment of the biogenic substance detection chip 1 according to the present technology.
  • the holding surface 111 is provided on the on-chip lens (OCL) 18 provided on the semiconductor substrate 12.
  • OCL on-chip lens
  • the specific configuration of the on-chip lens (OCL) 18 is not particularly limited, and the configuration of the on-chip lens (OCL) (antireflection layer etc.) can be freely selected and used.
  • the on-chip lens (OCL) 18 can be provided with a flattening film 19 as in the fourteenth embodiment shown in FIG.
  • the holding surface 111 can be provided on the flattening film 19 formed on the on-chip lens (OCL) 18.
  • OCL on-chip lens
  • the fourteenth embodiment shown in FIG. 21 includes a flattening film 19a for flattening the light shielding film 17 and a flattening film 19b for flattening the on-chip lens (OCL).
  • the flattening films 19a and 19b may be made of different materials or the same material.
  • FIG. 22 is a schematic cross-sectional view schematically showing a fifteenth embodiment of the biogenic substance detection chip 1 according to the present technology.
  • the biogenic substance detection chip 1 according to the fifteenth embodiment includes a protective film 20 on the chip surface.
  • the provision of the protective film 20 improves weather resistance to heat, light, water, acid, alkali, drug, etc., and allows contact with water, acid, alkali, or drug for a long period of time.
  • any material having weatherability against heat, light, water, acid, alkali, chemicals or the like can be freely selected and used according to the purpose.
  • silicon oxide (SiO 2 ), silicon nitride (Si 3 N 4 ), silicon oxynitride (SiON) and the like can be mentioned.
  • FIG. 23 is a schematic cross-sectional view schematically showing a sixteenth embodiment of the biogenic substance detection chip 1 according to the present technology.
  • the biogenic substance detection chip 1 according to the sixteenth embodiment includes an excitation light cut filter 21 on the chip surface. By including the excitation light cut filter 21, it is possible to prevent the excitation light from leaking into the photoelectric conversion unit 112. As a result, the detection accuracy can be further improved.
  • FIG. 24 is a schematic plan view from above showing a seventeenth embodiment of the biogenic substance detection chip 1 according to the present technology
  • FIG. 25 is a diagram with an internal structure omitted.
  • FIG. 24 is a schematic cross-sectional view taken along line AA of 24.
  • the biogenic substance detection chip 1 according to the seventeenth embodiment includes a step portion 22a on the outer side O of the effective pixel region 11E. More specifically, in the biogenic substance detection chip 1 according to the seventeenth embodiment, an intermediate region 22, a wiring region 23, and a peripheral region 24 are provided outward from the effective pixel region 11E, and the intermediate region 22 is provided. , A step 22a.
  • the wiring region 23 provided on the outside O of the effective pixel region 11E generally has a step, but in the seventeenth embodiment, a step is formed in the intermediate region 22 between the wiring region 23 and the effective pixel region 11E.
  • the corners of the step portion 22a are formed in an R shape in a top view.
  • the corners of the step portion 22a are formed into an R shape in a top view.
  • a stepped portion can be provided in the peripheral region 24.
  • the wiring region 23 is provided on the surface side of the chip 1 opposite to the holding surface 111 (light receiving surface), so that the unevenness of supply when the sample is supplied to the holding surface 111 and the holding surface 111. It is also possible to prevent cleaning defects and the like during cleaning.
  • FIG. 26 is a block diagram showing the concept of the biological material detection device 2 according to the present technology.
  • the biological substance detection device 2 according to the present technology includes at least the biological substance detection chip 1 according to the present technology described above, and the analysis unit 21. Further, the light irradiation unit 22, the storage unit 23, the display unit 24, the temperature control unit 25, and the like may be provided according to the purpose. Hereinafter, each part will be described. Since the biological substance detection chip 1 is as described above, the description thereof is omitted here.
  • the analysis unit 21 analyzes the electrical information acquired by the biogenic substance detection chip 1. For example, based on the electrical information acquired by the biogenic substance detection chip 1, presence/absence of the biogenic substance S, presence/absence of interaction in the biogenic substance S, screening of a medicinal component, and the like are performed.
  • the analysis unit 21 may be implemented by a personal computer or a CPU, and is stored as a program in a hardware resource including a recording medium (for example, non-volatile memory (USB memory), HDD, CD, etc.). It is also possible to make it function by a personal computer or a CPU.
  • a recording medium for example, non-volatile memory (USB memory), HDD, CD, etc.
  • the living body-derived substance detection device 2 can be provided with a light irradiation unit 22 for, for example, excitation light irradiation.
  • the light irradiation unit 22 irradiates the biological substance S held on the holding surface 111 of the biological substance detection chip 1 with light.
  • the light irradiation unit 22 is not essential, and the living body-derived substance S can be irradiated with light using an external light irradiation device or the like.
  • the type of light emitted from the light irradiation unit 22 is not particularly limited, but in order to reliably generate fluorescence or scattered light from fine particles, it is desirable that the light has a constant light direction, wavelength, and light intensity.
  • a laser, LED, etc. can be mentioned as an example.
  • the kind is not particularly limited, but an argon ion (Ar) laser, a helium-neon (He-Ne) laser, a die (dye) laser, a krypton (Cr) laser, a semiconductor laser, or a semiconductor laser is used.
  • argon ion (Ar) laser argon ion (Ar) laser
  • He-Ne helium-neon
  • He-Ne helium-neon
  • Cr krypton
  • semiconductor laser or a semiconductor laser is used.
  • One type or two or more types of solid-state lasers or the like combined with wavelength conversion optical elements can be freely combined and used.
  • a plurality of light irradiation units 22 may be provided according to the purpose.
  • one light irradiation unit 22 may be provided for each pixel 11 of the biogenic substance detection chip 1.
  • the biogenic substance S is obtained. It is also possible to irradiate this light.
  • the living body-derived substance detection device 2 may include a storage unit 23 that stores various types of information.
  • a storage unit 23 that stores various types of information.
  • all items related to detection such as electrical data acquired by the biogenic substance detection chip 1, analysis data generated by the analysis unit 21, optical data irradiated by the light irradiation unit 22, and the like. It is possible to store
  • the storage unit 23 is not essential, and an external storage device may be connected.
  • the storage unit 23 for example, a hard disk or the like can be used.
  • the living body-derived substance detection device 2 can include a display unit 24 that displays various types of information.
  • the electrical data acquired by the biogenic substance detection chip 1, the analysis data generated by the analysis unit 21, the optical data irradiated by the light irradiation unit 22, and the storage unit 23 are stored. All items related to detection such as data can be displayed.
  • the display unit 24 is not essential, and an external display device may be connected.
  • the display unit 24 for example, a display or a printer can be used.
  • Temperature control unit 25 The biogenic substance detection device 2 according to the present technology is for holding the biogenic substance S held on the holding surface 111 of the biogenic substance detection chip 1 at a predetermined temperature, or for heating or cooling to a predetermined temperature.
  • a temperature controller 25 can be provided.
  • the temperature control unit 25 can perform temperature control so as to maintain the optimum temperature.
  • the temperature control unit 25 can control the temperature so that the temperature range can be hybridized. ..
  • a thermoelectric element such as a Peltier element can be used.
  • a plurality of temperature control units 25 may be provided according to the purpose.
  • one temperature control unit 25 may be provided for each pixel 11 of the biogenic substance detection chip 1. Further, by stacking a substrate on which thermoelectric elements are arranged at positions corresponding to the respective pixels 11 of the biogenic substance detection chip 1 on the biogenic substance detection chip 1, temperature control of the biogenic substance S is performed. It is also possible to do.
  • the temperature control unit 25 is not essential in the biological substance detection device 2 according to the present technology, and the temperature of the biological substance S can be controlled using an external temperature control device or the like.
  • FIG. 27 is a block diagram showing the concept of the biological material detection system 3 according to the present technology.
  • the biogenic substance detection system 3 according to the present technology includes at least the biogenic substance detection chip 1 according to the present technology described above, and the analysis device 31. Further, the light irradiation device 32, the storage device 33, the display device 34, the temperature control device 35, and the like may be provided according to the purpose.
  • the biogenic substance detection chip 1 and each device can be connected via a wired or wireless network. Since the details of each device are the same as the details of each part of the biological substance detection device 2 in the present technology described above, the description thereof is omitted here.
  • the present technology may also have the following configurations.
  • the pixel includes at least a holding surface that holds a biological substance, and a photoelectric conversion unit that is provided below the holding surface and that is provided on a semiconductor substrate.
  • a biogenic substance detection chip in which a color mixture suppressing unit is provided between the pixels.
  • the biogenic substance detection chip according to (1), wherein the pixel and the color mixing suppression unit have different conductivity types.
  • the living body-derived substance detection chip according to (8) wherein the film has a first refractive index, and the semiconductor substrate has a second refractive index different from the first refractive index.
  • the biological substance is one or more biological substances selected from nucleic acids, proteins, cells, microorganisms, chromosomes, liposomes, mitochondria, organelles (organelles), and complexes thereof, (1) to ( The photodetection chip according to any one of 14).
  • the pixel includes at least a holding surface for holding a biological substance, and a photoelectric conversion unit provided below the holding surface, A color mixing suppression part is provided between the pixels, a chip for detecting a biological substance, An analysis unit that analyzes electrical information acquired by the biological substance detection chip, An apparatus for detecting a substance derived from a living body, comprising: (17) It consists of multiple pixels, The pixel includes at least a holding surface that holds a biological substance, and a photoelectric conversion unit provided below the holding surface, A color mixture suppressing part is provided between the pixels, and a biological substance detection chip, An analysis device for analyzing the electrical information acquired by the biogenic substance detection chip, A biological substance detection system comprising:

Abstract

The purpose of the present invention is to provide a chip for detecting a material derived from a living body with high detection accuracy. The present technology provides a chip for detecting a material derived from a living body, the chip comprising a plurality of pixels each of which is provided with at least: a holding surface for holding a material derived from a living body; and a photoelectric converting unit that is provided below the holding surface and is provided on a semiconductor substrate, wherein a color mixture suppressing unit is provided between the pixels. Also provided are an apparatus and system for detecting a material derived from a living body using said chip for detecting a material derived from the living body.

Description

生体由来物質検出用チップ、生体由来物質検出装置及び生体由来物質検出システムBiogenic substance detection chip, biogenic substance detection device, and biogenic substance detection system
　本技術は、生体由来物質検出用チップ、生体由来物質検出装置及び生体由来物質検出システムに関する。 The present technology relates to a biogenic substance detection chip, a biogenic substance detection device, and a biogenic substance detection system.
　近年、医療分野、創薬分野、臨床検査分野、食品分野、農業分野、工学分野等の様々な分野で、遺伝子解析、タンパク質解析、細胞解析等に関する技術研究が進められている。特に最近では、核酸、タンパク質、細胞、微生物等の生体由来物質の検出や解析等の各種反応を、チップに設けられたマイクロスケールの流路やウエル内で行うラボ・オン・チップを代表とするチップ上での検出技術の開発や実用化が進められている。これらは、生体由来物質等を簡便に計測する手法として注目を集めている。 In recent years, technical research on gene analysis, protein analysis, cell analysis, etc. has been advanced in various fields such as medical field, drug discovery field, clinical test field, food field, agricultural field, and engineering field. Especially recently, a lab-on-a-chip is a typical example, in which various reactions such as detection and analysis of biological substances such as nucleic acids, proteins, cells and microorganisms are carried out in microscale channels and wells provided on the chip. On-chip detection technology is being developed and put into practical use. These have attracted attention as a method for easily measuring substances derived from a living body.
　例えば、特許文献１では、複数のウエルが形成された第１の基板と、前記ウエルに接するように加熱手段が設けられた第２の基板と、前記各ウエルの位置に対応して位置決めされた複数の光照射手段が設けられた第３の基板と、前記各ウエルの位置に対応して位置決めされた複数の光検出手段が設けられた第４の基板と、が少なくとも備えられた光学的検出装置が開示されている。この光学的検出装置では、各ウエル中で進行する各種反応を測定することができる。 For example, in Patent Document 1, a first substrate having a plurality of wells formed therein, a second substrate provided with heating means so as to be in contact with the wells, and the wells are positioned corresponding to the positions of the respective wells. Optical detection including at least a third substrate provided with a plurality of light irradiation means and a fourth substrate provided with a plurality of light detection means positioned corresponding to the positions of the respective wells A device is disclosed. This optical detection device can measure various reactions progressing in each well.
　また、例えば、特許文献２では、光検出部が形成された基板と、前記基板に積層された、プラズモン吸収性を生じる金属ナノ構造を有するプラズモン吸収層と、を具備するケミカルセンサが開示されている。このケミカルセンサでは、センサ上に固定化されたプローブ材料とターゲット材料との結合に起因する発光を検出することができる。 Further, for example, Patent Document 2 discloses a chemical sensor including a substrate on which a photodetection portion is formed, and a plasmon absorption layer having a metal nanostructure that causes plasmon absorption and is stacked on the substrate. There is. With this chemical sensor, it is possible to detect the luminescence due to the bond between the probe material and the target material fixed on the sensor.
特開２０１０－２８４１５２号公報JP, 2010-284152, A ＷＯ２０１３／０８０４７３WO2013/080473
　チップ上の複数の領域（例えば、複数のウエル等）内において、生体関連物質から発せられる光を、各領域に対応する複数の光検出部を用いて検出する場合、各光検出部への隣接する領域からの光の漏れ込みの問題がある。例えば、各領域において、それぞれ異なる反応を進行させ、それぞれの反応に起因した発光を検出する場合、他の領域からの発光を誤って検出することにより、誤判定がなされる可能性がある。 When light emitted from a biological substance is detected in a plurality of regions (for example, a plurality of wells) on a chip by using a plurality of photodetection units corresponding to each region, it is adjacent to each photodetection unit. There is a problem of light leakage from the area to be illuminated. For example, when a different reaction is made to proceed in each region and light emission caused by each reaction is detected, there is a possibility that an erroneous determination is made by erroneously detecting the light emission from another region.
　そこで、本技術では、検出精度の高い生体由来物質検出用チップを提供することを主目的とする。 Therefore, the main purpose of the present technology is to provide a biogenic substance detection chip with high detection accuracy.
　即ち、本技術では、まず、複数の画素から構成され、
　前記画素は、生体由来物質を保持する保持表面と、前記保持表面の下方に設けられ、半導体基板に設けられた光電変換部と、を少なくとも備え、
　前記画素間には混色抑制部が設けられた、生体由来物質検出用チップを提供する。
　本技術に係る生体由来物質検出用チップにおいて、前記画素と前記混色抑制部とは異なる導電型とすることができる。
　この場合、前記画素はＮ型領域とし、前記混色抑制部はＰ型領域とすることができる。逆に、前記画素はＰ型領域とし、前記混色抑制部はＮ型領域とすることもできる。
　本技術に係る生体由来物質検出用チップにおいて、前記複数の画素は、各々、光電変換領域を有し、各光電変換領域間にトレンチを設けることができる。
　この場合、前記トレンチの内部に、酸化膜、及び金属から選択される１種以上を含ませることができる。
　本技術に係る生体由来物質検出用チップには、前記光電変換部の上方であって、前記保持表面に凹部を設けることができる。
　本技術に係る生体由来物質検出用チップにおいて、前記保持表面は、前記半導体基板上に形成された膜上に設けることができる。
　この場合、前記膜は第１の屈折率を有し、前記半導体基板は前記第１の屈折率とは異なる第２の屈折率を有していてもよい。
　また、前記膜は、無機膜、及び有機膜から選択される１以上の膜であってもよい。
　本技術に係る生体由来物質検出用チップには、隣接する前記画素間の上方に設けられた遮光膜を備えることができる。
　前記遮光膜間は、上面視において、円形、楕円形、及び角がＲ形状の多角形から選択される１以上の形状を呈するように成形することができる。
　本技術に係る生体由来物質検出用チップにおいて、前記保持表面は、前記半導体基板上に備えられたオンチップレンズ（ＯＣＬ）上に設けることができる。
　この場合、前記保持表面は、前記オンチップレンズ（ＯＣＬ）上に形成された平坦化膜上に設けることもできる。
　本技術に係る生体由来物質検出用チップが検出可能な生体由来物質としては、核酸、タンパク質、細胞、微生物、染色体、リポソーム、ミトコンドリア、オルガネラ（細胞小器官）、及びこれらの複合体から選択される１以上の生体由来物質を挙げることができる。 That is, in the present technology, first, it is composed of a plurality of pixels,
The pixel includes at least a holding surface that holds a biological substance, and a photoelectric conversion unit that is provided below the holding surface and that is provided on a semiconductor substrate.
Provided is a biogenic substance detection chip, in which a color mixture suppressing unit is provided between the pixels.
In the biogenic substance detection chip according to an embodiment of the present technology, the pixel and the color mixing suppression unit may have different conductivity types.
In this case, the pixel may be an N-type region and the color mixture suppressing unit may be a P-type region. On the contrary, the pixel may be a P-type region and the color mixture suppressing portion may be an N-type region.
In the biogenic substance detection chip according to the present technology, each of the plurality of pixels has a photoelectric conversion region, and a trench can be provided between the photoelectric conversion regions.
In this case, at least one selected from an oxide film and a metal may be included inside the trench.
In the biogenic substance detection chip according to the present technology, a recess may be provided on the holding surface above the photoelectric conversion unit.
In the chip for detecting a biological substance according to the present technology, the holding surface may be provided on a film formed on the semiconductor substrate.
In this case, the film may have a first refractive index, and the semiconductor substrate may have a second refractive index different from the first refractive index.
Further, the film may be one or more films selected from an inorganic film and an organic film.
The biogenic substance detection chip according to the present technology may include a light-shielding film provided above the adjacent pixels.
The space between the light shielding films may be formed to have one or more shapes selected from a circle, an ellipse, and a polygon having an R shape in a top view.
In the chip for detecting a biological substance according to the present technology, the holding surface may be provided on an on-chip lens (OCL) provided on the semiconductor substrate.
In this case, the holding surface may be provided on a flattening film formed on the on-chip lens (OCL).
The biogenic substance that can be detected by the biogenic substance detection chip according to the present technology is selected from nucleic acids, proteins, cells, microorganisms, chromosomes, liposomes, mitochondria, organelles (organelles), and complexes thereof. One or more biological materials can be mentioned.
　本技術では、次に、複数の画素から構成され、
前記画素は、生体由来物質を保持する保持表面と、前記保持表面の下方に設けられた光電変換部と、を少なくとも備え、
前記画素間には混色抑制部が設けられた、生体由来物質検出用チップと、
　前記生体由来物質検出用チップによって取得された電気的情報を解析する解析部と、
　を備える、生体由来物質検出装置を提供する。 In the present technology, next, it is composed of a plurality of pixels,
The pixel includes at least a holding surface for holding a biological substance, and a photoelectric conversion unit provided below the holding surface,
A color mixing suppression part is provided between the pixels, a chip for detecting a biological substance,
An analysis unit that analyzes electrical information acquired by the biological substance detection chip,
An apparatus for detecting a substance derived from a living body, comprising:
　本技術では、更に、複数の画素から構成され、
前記画素は、生体由来物質を保持する保持表面と、前記保持表面の下方に設けられた光電変換部と、を少なくとも備え、
前記画素間には混色抑制部が設けられた、生体由来物質検出用チップと、
　前記生体由来物質検出用チップによって取得された電気的情報を解析する解析装置と、
　を備える、生体由来物質検出システムを提供する。 The present technology further includes a plurality of pixels,
The pixel includes at least a holding surface for holding a biological substance, and a photoelectric conversion unit provided below the holding surface,
A color mixing suppression part is provided between the pixels, a chip for detecting a biological substance,
An analysis device that analyzes the electrical information acquired by the biogenic substance detection chip,
There is provided a biological substance detection system comprising:
　本技術において、「生体由来物質」には、核酸、タンパク質、細胞、微生物、染色体、リポソーム、ミトコンドリア、オルガネラ（細胞小器官）、及びこれらの複合体などが広く含まれるものとする。細胞には、動物細胞（血球系細胞など）および植物細胞が含まれる。微生物には、大腸菌などの細菌類、タバコモザイクウイルスなどのウイルス類、イースト菌などの菌類などが含まれる。 In the present technology, "living material" shall broadly include nucleic acids, proteins, cells, microorganisms, chromosomes, liposomes, mitochondria, organelles (organelles), complexes thereof, and the like. Cells include animal cells (such as blood cells) and plant cells. Microorganisms include bacteria such as Escherichia coli, viruses such as tobacco mosaic virus, fungi such as yeast.
本技術に係る生体由来物質検出用チップ１、生体由来物質検出装置２、及び生体由来物質検出システム３が検出することが可能な生体由来物質Ｓの相互作用を模式的に示す模式概念図である。FIG. 2 is a schematic conceptual diagram schematically showing the interaction of the biogenic substance S that can be detected by the biogenic substance detection chip 1, the biogenic substance detection device 2, and the biogenic substance detection system 3 according to the present technology. .. 本技術に係る生体由来物質検出用チップ１、生体由来物質検出装置２、及び生体由来物質検出システム３が検出することが可能な生体由来物質Ｓの相互作用を模式的に示す模式概念図である。FIG. 2 is a schematic conceptual diagram schematically showing the interaction of the biogenic substance S that can be detected by the biogenic substance detection chip 1, the biogenic substance detection device 2, and the biogenic substance detection system 3 according to the present technology. .. 本技術に係る生体由来物質検出用チップ１、生体由来物質検出装置２、及び生体由来物質検出システム３が検出することが可能な生体由来物質Ｓの相互作用を模式的に示す模式概念図である。FIG. 2 is a schematic conceptual diagram schematically showing the interaction of the biogenic substance S that can be detected by the biogenic substance detection chip 1, the biogenic substance detection device 2, and the biogenic substance detection system 3 according to the present technology. .. 本技術に係る生体由来物質検出用チップ１、生体由来物質検出装置２、及び生体由来物質検出システム３が行うことが可能な他の物質のスクリーニングを模式的に示す模式概念図である。It is a schematic conceptual diagram which shows typically the screening of the other substance which can be performed by the biogenic substance detection chip 1, the biogenic substance detection device 2, and the biogenic substance detection system 3 according to the present technology. 本技術に係る生体由来物質検出用チップ１、生体由来物質検出装置２、及び生体由来物質検出システム３が行うことが可能な他の物質のスクリーニングを模式的に示す模式概念図である。It is a schematic conceptual diagram which shows typically the screening of the other substance which can be performed by the biogenic substance detection chip 1, the biogenic substance detection device 2, and the biogenic substance detection system 3 according to the present technology. 本技術に係る生体由来物質検出用チップ１、生体由来物質検出装置２、及び生体由来物質検出システム３が行うことが可能な他の物質のスクリーニングを模式的に示す模式概念図である。It is a schematic conceptual diagram which shows typically the screening of the other substance which can be performed by the biogenic substance detection chip 1, the biogenic substance detection device 2, and the biogenic substance detection system 3 according to the present technology. 本技術に係る生体由来物質検出用チップ１の第１実施形態を模式的に示す模式断面図である。It is a schematic cross section which shows typically 1st Embodiment of the chip|tip 1 for biogenic substance detection which concerns on this technique. Ａは、本技術に係る生体由来物質検出用チップ１の第２実施形態を模式的に示す模式端面図であり、Ｂは、第２実施形態の変形例を模式的に示す模式断面図である。A is a schematic end view schematically showing a second embodiment of the biogenic substance detection chip 1 according to the present technology, and B is a schematic cross-sectional view schematically showing a modified example of the second embodiment. .. 本技術に係る生体由来物質検出用チップ１の第３実施形態を模式的に示す模式断面図である。It is a schematic cross section which shows typically 3rd Embodiment of the chip|tip 1 for biogenic substance detection which concerns on this technique. 本技術に係る生体由来物質検出用チップ１の第４実施形態を模式的に示す模式断面図である。It is a schematic cross section which shows typically 4th Embodiment of the chip|tip 1 for biogenic substance detection which concerns on this technique. 本技術に係る生体由来物質検出用チップ１の第５実施形態を模式的に示す模式断面図である。It is a schematic cross section which shows typically 5th Embodiment of the chip|tip 1 for biogenic substance detection which concerns on this technique. 本技術に係る生体由来物質検出用チップ１の第６実施形態を模式的に示す模式断面図である。It is a schematic cross section which shows typically 6th Embodiment of the chip|tip 1 for biological substance detection which concerns on this technique. 本技術に係る生体由来物質検出用チップ１の第７実施形態を模式的に示す模式断面図である。It is a schematic cross section which shows typically 7th Embodiment of the chip|tip 1 for biogenic substance detection which concerns on this technique. 本技術に係る生体由来物質検出用チップ１の第８実施形態を模式的に示す模式断面図である。It is a schematic cross section which shows typically 8th Embodiment of the chip|tip 1 for biogenic substance detection which concerns on this technique. 本技術に係る生体由来物質検出用チップ１の第９実施形態を模式的に示す模式断面図である。It is a schematic cross section which shows typically 9th Embodiment of the chip|tip 1 for biogenic substance detection which concerns on this technique. 本技術に係る生体由来物質検出用チップ１の遮光膜１７の例を模式的に示す上方視模式平面図である。It is an upper side view schematic plan view which shows typically the example of the light shielding film 17 of the chip|tip 1 for biogenic substance detection which concerns on this technique. 本技術に係る生体由来物質検出用チップ１の第１０実施形態を模式的に示す模式断面図である。It is a schematic cross section which shows typically 10th Embodiment of the chip|tip 1 for biogenic substance detection which concerns on this technique. 本技術に係る生体由来物質検出用チップ１の第１１実施形態を模式的に示す模式断面図である。It is a schematic cross section which shows typically 11th Embodiment of the chip|tip 1 for biogenic substance detection which concerns on this technique. 本技術に係る生体由来物質検出用チップ１の第１２実施形態を模式的に示す模式断面図である。It is a schematic cross section which shows typically 12th Embodiment of the chip|tip 1 for biogenic substance detection which concerns on this technique. 本技術に係る生体由来物質検出用チップ１の第１３実施形態を模式的に示す模式断面図である。It is a schematic cross section which shows typically 13th Embodiment of the chip|tip 1 for biogenic substance detection which concerns on this technique. 本技術に係る生体由来物質検出用チップ１の第１４実施形態を模式的に示す模式断面図である。It is a schematic cross section which shows typically 14th Embodiment of the chip|tip 1 for biological substance detection which concerns on this technique. 本技術に係る生体由来物質検出用チップ１の第１５実施形態を模式的に示す模式断面図である。It is a schematic cross section which shows typically 15th Embodiment of the chip|tip 1 for biological substance detection which concerns on this technique. 本技術に係る生体由来物質検出用チップ１の第１６実施形態を模式的に示す模式断面図である。It is a schematic cross section which shows typically 16th Embodiment of the chip|tips 1 for biogenic substance detection which concerns on this technique. 本技術に係る生体由来物質検出用チップ１の第１７実施形態を模式的に示す上方視模式平面図である。It is an upper side view schematic plan view which shows typically the 17th Embodiment of the chip|tip 1 for biogenic substance detection which concerns on this technique. 内部構造を省略した図２４のＡ－Ａ視断面模式図である。FIG. 25 is a schematic cross-sectional view taken along the line AA of FIG. 24 in which the internal structure is omitted. 本技術に係る生体由来物質検出装置２の概念を示すブロック図である。It is a block diagram which shows the concept of the biological substance detection apparatus 2 which concerns on this technique. 本技術に係る生体由来物質検出システム３の概念を示すブロック図である。It is a block diagram which shows the concept of the biological substance detection system 3 which concerns on this technique.
　以下、本技術を実施するための好適な形態について図面を参照しながら説明する。以下に説明する実施形態は、本技術の代表的な実施形態の一例を示したものであり、これにより本技術の範囲が狭く解釈されることはない。なお、説明は以下の順序で行う。
　１．本技術で行う生体由来物質検出の概要
　（１）生体由来物質Ｓのそのものの検出
　（２）生体由来物質Ｓの相互作用の検出
　（３）他の物質のスクリーニング
　２．生体由来物質検出用チップ１
　（１）第１実施形態
　（２）第２実施形態、第３実施形態
　（３）第４実施形態
　（４）第５実施形態～第７実施形態
　（５）第９実施形態～第１２実施形態
　（６）第１３実施形態、第１４実施形態
　（７）第１５実施形態
　（８）第１６実施形態
　（９）第１７実施形態
　３．生体由来物質検出装置２
　４．生体由来物質検出システム３ Hereinafter, a suitable mode for carrying out the present technology will be described with reference to the drawings. The embodiment described below shows an example of a typical embodiment of the present technology, and the scope of the present technology is not narrowly construed by this. The description will be given in the following order.
1. 1. Outline of detection of biogenic substance performed by the present technology (1) Detection of biogenic substance S itself (2) Detection of interaction of biogenic substance S (3) Screening of other substances Chip 1 for detecting biological substances
(1) First embodiment (2) Second embodiment, third embodiment (3) Fourth embodiment (4) Fifth embodiment to seventh embodiment (5) Ninth embodiment to twelfth embodiment (6) 13th embodiment, 14th embodiment (7) 15th embodiment (8) 16th embodiment (9) 17th embodiment 3. Biological substance detection device 2
4. Biological substance detection system 3
＜１．本技術で行う生体由来物質検出の概要＞
　本技術に係る生体由来物質検出用チップ１、生体由来物質検出装置２、及び生体由来物質検出システム３が行う生体由来物質Ｓの検出の概要を説明する。本技術に係る生体由来物質検出用チップ１、生体由来物質検出装置２、及び生体由来物質検出システム３は、（１）生体由来物質Ｓのそのものの検出、（２）生体由来物質Ｓの相互作用の検出、（３）生体由来物質Ｓを用いた他の物質（例えば、薬効成分等）のスクリーニング等に用いることができる。なお、各検出は、後述する生体由来物質検出用チップ１の保持表面１１１にて行われる。 <1. Overview of detection of biological substances by this technology>
The outline of the detection of the biogenic substance S performed by the biogenic substance detection chip 1, the biogenic substance detection device 2, and the biogenic substance detection system 3 according to the present technology will be described. The biogenic substance detection chip 1, the biogenic substance detection device 2, and the biogenic substance detection system 3 according to the present technology include (1) detection of the biogenic substance S itself, and (2) interaction of the biogenic substance S. And (3) screening of other substances (for example, medicinal components) using the biogenic substance S. In addition, each detection is performed on the holding surface 111 of the biogenic substance detection chip 1 described later.
　（１）生体由来物質Ｓのそのものの検出
　例えば、血液、尿、便、唾液等の体液中に含まれる赤血球、白血球、血小板、サイトカイン、ホルモン物質、糖、脂質、タンパク質等の生体物質；体液や水中に含まれる細菌類、菌類、ウイルス等の微生物；細胞や微生物中の遺伝子等の検出に、本技術を用いることができる。例えば、検出対象の物質あるいは非検出対象の物質に特異的に作用する色素を用いて染色した後、目的の光検出の有無によって、検出対象の物質の存在を検出することができる。検出された結果は、疾患の診断、体内環境診断、水質検査等に用いることができる。 (1) Detection of the body-derived substance S itself For example, biological substances such as red blood cells, white blood cells, platelets, cytokines, hormonal substances, sugars, lipids and proteins contained in body fluids such as blood, urine, feces and saliva; The present technology can be used for detecting microorganisms such as bacteria, fungi, and viruses contained in water; genes in cells and microorganisms. For example, the presence of the substance to be detected can be detected by the presence or absence of the desired light detection after dyeing with a dye that specifically acts on the substance to be detected or the substance not to be detected. The detected results can be used for diagnosis of diseases, internal environment diagnosis, water quality test and the like.
　（２）生体由来物質Ｓの相互作用の検出
　例えば、タンパク質の相互作用、核酸のハイブリダイゼーション、サイトカインやホルモン物質と受容体との結合等の相互作用の検出に、本技術を用いることができる。具体的な検出例について、図１～３を用いて説明する。 (2) Detection of interaction of biological substance S For example, the present technology can be used for detection of interaction such as protein interaction, nucleic acid hybridization, and binding between cytokine or hormone substance and receptor. A specific detection example will be described with reference to FIGS.
　例えば、図１のＡ～Ｄに示すように、保持表面１１１にタンパク質や受容体（あるいは受容体を模したもの）等の生体由来物質Ｓ１を固定しておき（図１中Ａ参照）、これとの相互作用を確認する生体由来物質Ｓ２～Ｓ４に蛍光Ｆ１～Ｆ３等の色素を固定したものを加える（図１中Ｂ参照）。そして、相互作用しなかった生体由来物質Ｓ３及びＳ４の洗浄を行い（図１中Ｃ参照）、保持表面１１１から蛍光Ｆ１を検出することで（図１中Ｄ参照）、生体由来物質Ｓ１と生体由来物質Ｓ２との相互作用を検出することができる。 For example, as shown in FIGS. 1A to 1D, a biological substance S1 such as a protein or a receptor (or a model imitating a receptor) is immobilized on the holding surface 111 (see A in FIG. 1). A substance in which a dye such as fluorescence F1 to F3 is immobilized is added to the biogenic substances S2 to S4 for confirming the interaction with (see B in FIG. 1). Then, the biological substances S3 and S4 that have not interacted with each other are washed (see C in FIG. 1), and the fluorescence F1 is detected from the holding surface 111 (see D in FIG. 1), whereby the biological substance S1 and the biological substance The interaction with the derived substance S2 can be detected.
　例えば、図１のＥ～Ｈに示すように、保持表面１１１に細胞等の生体由来物質Ｓ１を固定しておき、この生体由来物質Ｓ１が有する輸送体ｔ（例えば、細胞膜中のトランスポーター等）を介して取り込まれる発光体Ｆ１を検知することができる。 For example, as shown in E to H of FIG. 1, a biogenic substance S1 such as cells is immobilized on the holding surface 111, and the transporter t of the biogenic substance S1 (for example, a transporter in a cell membrane). It is possible to detect the illuminant F1 that is taken in through.
　例えば、図２のＡ～Ｄに示すように、保持表面１１１にＤＮＡやＲＮＡ等からなるプローブＳ５を固定しておき（図２中Ａ参照）、ターゲットとなり得るＤＮＡＳ６及びＳ７を含むサンプルと、インターカレーターＩとを加える（図２中Ｂ参照）。そして、プローブＳ５と相補的な配列を有するＤＮＡＳ６が、サンプルに含有されていると、ハイブリダーゼーション反応が起きる。ハイブリダーゼーションが行われなかったＤＮＡＳ７の洗浄を行い（図２中Ｃ参照）、保持表面１１１からインターカレーターＩからの光を検出することで（図２中Ｄ参照）、プローブＳ５とターゲットＤＮＡＳ６とのハイブリダーゼーションを検出することができる。 For example, as shown in FIGS. 2A to 2D, a probe S5 made of DNA, RNA or the like is immobilized on the holding surface 111 (see A in FIG. 2), and a sample containing DNAs S6 and S7 that can be targets and Add Calculator I (see B in Figure 2). Then, when DNA S6 having a sequence complementary to probe S5 is contained in the sample, a hybridization reaction occurs. By washing the DNAS7 that has not been hybridized (see C in FIG. 2) and detecting the light from the intercalator I from the holding surface 111 (see D in FIG. 2), the probe S5 and the target DNAS6 are detected. Hybridization can be detected.
　例えば、図３のＡ～Ｄに示すように、保持表面１１１に生体由来物質Ｓ８を固定しておき（図３中Ａ参照）、これと相互作用して新たな物質Ｓ１０になる生体由来物質Ｓ９を加える（図３中Ｂ参照）。次に、物質Ｓ１０に特異的に結合する蛍光Ｆ４等の色素を加え（図３中Ｃ参照）、保持表面１１１から蛍光Ｆ４を検出することで（図３中Ｄ参照）、生体由来物質Ｓ８と生体由来物質Ｓ９との相互作用を検出することができる。 For example, as shown in FIGS. 3A to 3D, the biogenic substance S8 is fixed on the holding surface 111 (see A in FIG. 3), and interacts with this to form a new substance S10, the biogenic substance S9. Is added (see B in FIG. 3). Next, a dye such as fluorescent F4 that specifically binds to the substance S10 is added (see C in FIG. 3), and the fluorescent F4 is detected from the holding surface 111 (see D in FIG. 3) to obtain the biologically derived substance S8. The interaction with the biological substance S9 can be detected.
　（３）他の物質のスクリーニング
　例えば、各種受容体の作動薬（アゴニスト）や拮抗薬（アンタゴニスト）となり得る物質のスクリーニングや、各種微生物の産生抑制剤、抗菌剤、殺菌剤等のスクリーニングに、本技術を用いることができる。具体的な検出例について、図４～図６を用いて説明する。 (3) Screening for other substances For example, for screening for substances that can be agonists (agonists) or antagonists (antagonists) of various receptors, and for screening various microorganism production inhibitors, antibacterial agents, bactericides, etc. Technology can be used. A specific detection example will be described with reference to FIGS. 4 to 6.
　例えば、図４のＡ～Ｄに示すように、保持表面１１１に受容体Ｒ１（あるいは受容体Ｒ１を模したもの）を固定しておき（図４中Ａ参照）、この受容体Ｒ１の作動性を確認する物質ｄ１～ｄ３に蛍光Ｆ５～Ｆ７等の色素を固定したものを加える（図４中Ｂ参照）。そして、受容体Ｒ１に結合しなかった物質ｄ２及びｄ３の洗浄を行い（図４中Ｃ参照）、保持表面１１１から蛍光Ｆ５を検出することで（図３中Ｄ参照）、受容体Ｒ１の作動薬となり得る物質ｄ１のスクリーニングを行うことができる。 For example, as shown in FIGS. 4A to 4D, the receptor R1 (or a model imitating the receptor R1) is fixed to the holding surface 111 (see A in FIG. 4), and the operability of the receptor R1 is increased. To the substances d1 to d3 for confirming the above, dyes such as fluorescent dyes F5 to F7 immobilized are added (see B in FIG. 4). Then, the substances d2 and d3 that have not bound to the receptor R1 are washed (see C in FIG. 4), and the fluorescence F5 is detected from the holding surface 111 (see D in FIG. 3) to activate the receptor R1. It is possible to screen the substance d1 which can be a drug.
　例えば、図５のＡ～Ｅに示すように、保持表面１１１に受容体Ｒ２（あるいは受容体Ｒ２を模したもの）を固定しておき（図５中Ａ参照）、この受容体Ｒ２の拮抗性を確認する物質ｄ４を加える（図５中Ｂ参照）。次に、蛍光Ｆ８等の色素を固定した受容体Ｒ２と結合するリガンドＬ１を加える（図５中Ｃ参照）。この時、物質ｄ４が受容体Ｒ２の拮抗薬となり得る場合は、既に、受容体Ｒ２と物質ｄ４が結合等しているため、リガンドＬ１は、受容体Ｒ２に結合することができない（図５中Ｃ参照）。この状態で、受容体Ｒ２に結合しなかったリガンドＬ１の洗浄を行った後（図５中Ｄ参照）、保持表面１１１から蛍光Ｆ８を検出しようとしても、蛍光Ｆ８は洗浄により保持表面１１１に存在しないため、光検出がされない（図５中Ｅ参照）。 For example, as shown in FIGS. 5A to 5E, the receptor R2 (or a model imitating the receptor R2) is immobilized on the holding surface 111 (see A in FIG. 5), and the receptor R2 has an antagonistic property. The substance d4 for confirming is confirmed (see B in FIG. 5). Next, a ligand L1 that binds to the receptor R2 on which a dye such as fluorescent F8 is immobilized is added (see C in FIG. 5). At this time, if the substance d4 can be an antagonist of the receptor R2, the ligand L1 cannot bind to the receptor R2 because the receptor R2 and the substance d4 are already bound (see FIG. 5). (See C). In this state, after washing the ligand L1 which did not bind to the receptor R2 (see D in FIG. 5), even if an attempt is made to detect the fluorescence F8 from the holding surface 111, the fluorescence F8 is present on the holding surface 111 by washing. Since no light is detected, no light is detected (see E in FIG. 5).
　一方、例えば、図６のＡ～Ｅに示すように、保持表面１１１に受容体Ｒ３（あるいは受容体Ｒ３を模したもの）を固定しておき（図６中Ａ参照）、この受容体Ｒ３の拮抗性を確認する物質ｄ５を加える（図６中Ｂ参照）。次に、蛍光Ｆ９等の色素を固定した受容体Ｒ３と結合するリガンドＬ２を加える（図６中Ｃ参照）。この時、物質ｄ５が受容体Ｒ３の拮抗薬となり得ない場合は、リガンドＬ２は、受容体Ｒ３に結合する（図６中Ｄ参照）。この状態で、受容体Ｒ３に結合しなかった物質ｄ５の洗浄を行うと（図６中Ｄ参照）、保持表面１１１から蛍光Ｆ９が検出される（図６中Ｅ参照）。 On the other hand, for example, as shown in FIGS. 6A to 6E, the receptor R3 (or a model imitating the receptor R3) is fixed to the holding surface 111 (see A in FIG. 6), and the receptor R3 A substance d5 for confirming antagonisticity is added (see B in FIG. 6). Next, a ligand L2 that binds to a receptor R3 having a dye such as fluorescent F9 immobilized thereon is added (see C in FIG. 6). At this time, when the substance d5 cannot be an antagonist of the receptor R3, the ligand L2 binds to the receptor R3 (see D in FIG. 6). In this state, when the substance d5 that has not bound to the receptor R3 is washed (see D in FIG. 6), fluorescence F9 is detected from the holding surface 111 (see E in FIG. 6).
　このように、図５及び図６に示すように、保持表面１１１から蛍光Ｆ８又は蛍光Ｆ９の検出の有無によって、受容体Ｒ３の拮抗薬となり得る物質ｄ４のスクリーニングを行うことができる。 As described above, as shown in FIGS. 5 and 6, the substance d4 that can be an antagonist of the receptor R3 can be screened depending on whether or not the fluorescence F8 or the fluorescence F9 is detected from the holding surface 111.
＜２．生体由来物質検出用チップ１＞
　本技術に係る生体由来物質検出用チップ１は、複数の画素１１から構成され、画素１１は、生体由来物質Ｓを保持する保持表面１１１と、保持表面１１１の下方に設けられ、半導体基板１２に設けられた光電変換部１１２を少なくとも備える。そして、各画素１１間には、混色抑制部１３が設けられている。以下、各実施形態を参照しながら、説明する。 <2. Bio-derived substance detection chip 1>
The biogenic substance detection chip 1 according to an embodiment of the present technology includes a plurality of pixels 11. The pixel 11 is provided on a holding surface 111 that holds the biogenic substance S, and is provided below the holding surface 111. At least the provided photoelectric conversion unit 112 is provided. A color mixture suppression unit 13 is provided between each pixel 11. Hereinafter, description will be made with reference to each embodiment.
　（１）第１実施形態
　図７は、本技術に係る生体由来物質検出用チップ１の第１実施形態を模式的に示す模式断面図である。第１実施形態に係る生体由来物質検出用チップ１は、複数の画素１１が行列状に２次元配置された有効画素領域１１Ｅを備える。各画素１１は、生体由来物質Ｓを保持する保持表面１１１と、光電変換部１１２と、を少なくとも備える。光電変換部１１２には、例えば、フォトダイオードのような光電変換素子を自由に用いることができる。また、図示しないが、各画素１１には、電荷蓄積部、複数のトランジスタ、及び容量素子等で構成された画素回路を備えていても良い。有効画素領域１１Ｅの外側Ｏには、図示しないが、光学的黒画素や配線領域等を備えることができる。 (1) First Embodiment FIG. 7 is a schematic cross-sectional view schematically showing a first embodiment of the biogenic substance detection chip 1 according to the present technology. The biogenic substance detection chip 1 according to the first embodiment includes an effective pixel region 11E in which a plurality of pixels 11 are two-dimensionally arranged in a matrix. Each pixel 11 includes at least a holding surface 111 that holds the biological substance S and a photoelectric conversion unit 112. For the photoelectric conversion unit 112, for example, a photoelectric conversion element such as a photodiode can be freely used. Although not shown, each pixel 11 may include a pixel circuit including a charge storage section, a plurality of transistors, a capacitive element, and the like. Although not shown, an optical black pixel, a wiring region, or the like can be provided on the outside O of the effective pixel region 11E.
　保持表面１１１は、生体由来物質Ｓが保持できる構成であれば特に限定されず、表面処理を自由に用いることができる。例えば、紫外線照射により親水性に変性する感光性シランカップリング剤等を塗布し、生体由来物質Ｓを保持したい領域を選択的に紫外線照射することにより、保持表面１１１を形成することができる。また、例えば、保持表面１１１をアビジン処理しておくことで、その一端がビオチン化された核酸等の生体由来物質Ｓを、アビジン－ビオチン結合により、保持することもできる。 The holding surface 111 is not particularly limited as long as it can hold the biological substance S, and surface treatment can be freely used. For example, the holding surface 111 can be formed by applying a photosensitive silane coupling agent or the like that is hydrophilically modified by irradiation with ultraviolet rays and selectively irradiating the area where the biological substance S is desired to be retained with ultraviolet rays. Further, for example, by treating the holding surface 111 with avidin, a biological substance S such as a nucleic acid having one end thereof biotinylated can be held by avidin-biotin bond.
　また、後述する遮光膜１７や隔壁等を、隣接する画素１１間の上方（チップ表面上側）に設け、チップ１表面に液体を保持できる構成とすることで、液体中に生体由来物質Ｓを保持することも可能である。 Further, by providing a light-shielding film 17, a partition wall, and the like, which will be described later, between adjacent pixels 11 (on the upper side of the chip surface) so that the liquid can be held on the surface of the chip 1, the biological substance S is held in the liquid. It is also possible to do so.
　各画素１１間には、混色抑制部１３が設けられている。本技術に係る生体由来物質検出用チップ１の第１実施形態では、画素１１と混色抑制部１３とを、異なる導電型とすることにより、隣接する画素１１間における混色を抑制する。具体的には、例えば、画素１１をＮ型領域とし、各画素１１間をＰ型領域としたり、逆に、画素１１をＰ型領域とし、各画素１１間をＮ型領域とすることで、隣接する画素１１間における混色を抑制することができる。 A color mixture suppression unit 13 is provided between each pixel 11. In the first embodiment of the biogenic substance detection chip 1 according to the present technology, the pixels 11 and the color mixing suppression unit 13 have different conductivity types, thereby suppressing color mixing between the adjacent pixels 11. Specifically, for example, the pixels 11 are N-type regions and the pixels 11 are P-type regions, or conversely, the pixels 11 are P-type regions and the pixels 11 are N-type regions. Color mixing between adjacent pixels 11 can be suppressed.
　なお、図７に示す第１実施形態には、説明のために、生体由来物質Ｓを記載しているが、本技術に係る生体由来物質検出用チップ１には、生体由来物質Ｓは包含されない。 In addition, in the first embodiment shown in FIG. 7, the biogenic substance S is described for the sake of explanation, but the biogenic substance detection chip 1 according to the present technology does not include the biogenic substance S. ..
　（２）第２実施形態、第３実施形態
　図８Ａは、本技術に係る生体由来物質検出用チップ１の第２実施形態を模式的に示す模式端面図であり、図８Ｂは、第２実施形態の変形例を模式的に示す模式断面図である。第２実施形態に係る生体由来物質検出用チップ１は、光電変換領域１１２Ａ間にトレンチ１３Ｔを備え、このトレンチ１３Ｔが、混色抑制部１３として機能する。 (2) Second Embodiment, Third Embodiment FIG. 8A is a schematic end view schematically showing a second embodiment of the biogenic substance detection chip 1 according to the present technology, and FIG. 8B shows the second embodiment. It is a schematic cross section which shows the modification of a form typically. The biogenic substance detection chip 1 according to the second embodiment includes trenches 13T between the photoelectric conversion regions 112A, and the trenches 13T function as the color mixing suppression unit 13.
　トレンチ１３Ｔ内部には、図８Ｂに示すように、酸化膜１４を設けることができる。酸化膜１４の材料としては、例えば、酸化ハフニウム（ＨｆＯ２）、酸化アルミニウム（Ａｌ２Ｏ３）、酸化タンタル（Ｔａ２Ｏ５）等の負の固定電荷を有する材料が挙げられる。これらの酸化膜を単膜で設けても良いし、複数の膜を重ねて設けても良い。酸化膜を設けることにより暗電流を抑制することができ、誤判定を抑制することができる。 An oxide film 14 can be provided inside the trench 13T as shown in FIG. 8B. Examples of the material of the oxide film 14 include materials having a negative fixed charge such as hafnium oxide (HfO 2 ), aluminum oxide (Al 2 O 3 ), and tantalum oxide (Ta 2 O 5 ). These oxide films may be provided as a single film or a plurality of films may be stacked. By providing the oxide film, dark current can be suppressed and erroneous determination can be suppressed.
　トレンチ１３Ｔの内部には、図９に示す第３実施形態のように、酸化膜１４及び金属１５等を備えることができる。金属１５を設けることにより、遮光効果を高めて、隣接画素への混色を抑制することができ、誤判定を抑制することができる。トレンチ１３Ｔ内部に酸化膜１４及び金属１５を備えることで、暗電流を抑制しつつも隣接する画素１１間における混色抑制効果を向上させることができる。 Inside the trench 13T, as in the third embodiment shown in FIG. 9, an oxide film 14 and a metal 15 can be provided. By providing the metal 15, it is possible to enhance the light blocking effect, suppress color mixture to adjacent pixels, and suppress erroneous determination. By providing the oxide film 14 and the metal 15 inside the trench 13T, it is possible to improve the color mixture suppressing effect between the adjacent pixels 11 while suppressing the dark current.
　酸化膜１４としては、図８で説明した酸化膜を用いることができる。すなわち、酸化シリコン膜（ＳｉＯ２膜）、酸化ハフニウム膜（ＨｆＯ２膜）、酸化アルミニウム膜（Ａｌ２Ｏ３膜）、酸化タンタル膜（Ｔａ２Ｏ５膜）等を挙げることができる。 As the oxide film 14, the oxide film described with reference to FIG. 8 can be used. That is, a silicon oxide film (SiO 2 film), a hafnium oxide film (HfO 2 film), an aluminum oxide film (Al 2 O 3 film), a tantalum oxide film (Ta 2 O 5 film), and the like can be given.
　金属としては、例えば、タングステン（Ｗ）、アルミニウム（Ａｌ）、銅（Ｃｕ）、チタン（Ｔｉ）等を用いることができる。 As the metal, for example, tungsten (W), aluminum (Al), copper (Cu), titanium (Ti) or the like can be used.
　なお、第２実施形態及び第３実施形態において、その他の構造は、前述した第１実施形態と同一であるため、ここでは説明を割愛する。以下、他の実施形態においても、第１実施形態と異なる部分のみ説明する。 The other structures of the second and third embodiments are the same as those of the first embodiment described above, and therefore the description thereof is omitted here. Hereinafter, also in the other embodiments, only parts different from the first embodiment will be described.
　（３）第４実施形態
　図１０Ａは、本技術に係る生体由来物質検出用チップ１の第４実施形態を模式的に示す模式断面図である。第４実施形態に係る生体由来物質検出用チップ１は、光電変換部１１２の上方であって、保持表面１１１に凹部１１１Ｃが設けられている。この凹部１１１Ｃに、検出対象となる生体由来物質Ｓを保持することで、生体由来物質Ｓからの光の散乱を防止することができる。 (3) Fourth Embodiment FIG. 10A is a schematic cross-sectional view schematically showing a fourth embodiment of the biogenic substance detection chip 1 according to the present technology. The living body-derived substance detection chip 1 according to the fourth embodiment has a recess 111C on the holding surface 111 above the photoelectric conversion unit 112. By holding the biogenic substance S to be detected in the recess 111C, it is possible to prevent light from being scattered from the biogenic substance S.
　凹部１１１Ｃには、図１０Ｂに示すように、酸化膜１４を備えることができる。酸化膜１４を備えることで、混色経路を無くし感度を向上することができる。 The recess 111C can be provided with an oxide film 14 as shown in FIG. 10B. By providing the oxide film 14, it is possible to eliminate the color mixing path and improve the sensitivity.
　また、凹部１１１Ｃの形状は特に限定されず、図１０Ａ及びＢに示すような断面視略三角形状の他に、図１０Ｃに示すような断面視略四角形状や断面視略台形形状、図示しないが、断面視略半円形状等に設計することができる。 The shape of the concave portion 111C is not particularly limited, and in addition to the substantially triangular shape in cross section as shown in FIGS. 10A and 10B, the substantially rectangular shape in cross section as shown in FIG. It can be designed in a substantially semicircular shape in cross section.
　（４）第５実施形態～第７実施形態
　図１１は、本技術に係る生体由来物質検出用チップ１の第５実施形態を模式的に示す模式断面図である。第５実施形態に係る生体由来物質検出用チップ１は、保持表面１１１が、半導体基板１２上に形成された膜１６上に設けられている。 (4) Fifth Embodiment to Seventh Embodiment FIG. 11 is a schematic cross-sectional view schematically showing a fifth embodiment of the biogenic substance detection chip 1 according to the present technology. In the biogenic substance detection chip 1 according to the fifth embodiment, the holding surface 111 is provided on the film 16 formed on the semiconductor substrate 12.
　膜１６としては、半導体基板１２上に形成される膜を、目的に応じて１種又は２種以上自由に選択することができる。例えば、酸化シリコン膜（ＳｉＯ２膜）、窒化シリコン膜（Ｓｉ３Ｎ４膜）、シリコン酸窒化膜（ＳｉＯＮ膜）、酸化ハフニウム膜（ＨｆＯ膜）、酸化アルミニウム膜（Ａｌ２Ｏ３膜）、酸化タンタル膜（Ｔａ２Ｏ５膜）等の無機膜や、スチレン系樹脂、アクリル系樹脂、スチレン－アクリル共重合系樹脂、またはシロキサン系樹脂等の樹脂系材料からなる有機膜等を挙げることができる。 As the film 16, one kind or two or more kinds of films formed on the semiconductor substrate 12 can be freely selected according to the purpose. For example, a silicon oxide film (SiO 2 film), a silicon nitride film (Si 3 N 4 film), a silicon oxynitride film (SiON film), a hafnium oxide film (HfO film), an aluminum oxide film (Al 2 O 3 film), Examples thereof include an inorganic film such as a tantalum oxide film (Ta 2 O 5 film), an organic film made of a resin material such as a styrene resin, an acrylic resin, a styrene-acryl copolymer resin, or a siloxane resin. it can.
　膜１６の屈折率は、半導体基板１２の屈折率と異なることが好ましい。換言すると、膜１６は第１の屈折率を有し、半導体基板１２は前記第１の屈折率とは異なる第２の屈折率を有することが好ましい。膜１６の屈折率と、半導体基板１２の屈折率とが異なることで、反射率の角度依存の光学設計が可能となり、保持表面１１１に保持された生体由来物質Ｓからの光のうち、横方向の光を反射させて半導体基板１２内に入射するのを防止することができ、その結果、画素１１間における混色を防止することができる。 The refractive index of the film 16 is preferably different from that of the semiconductor substrate 12. In other words, it is preferable that the film 16 has a first refractive index and the semiconductor substrate 12 has a second refractive index different from the first refractive index. Since the refractive index of the film 16 and the refractive index of the semiconductor substrate 12 are different from each other, an angle-dependent optical design of the reflectance can be performed, and the lateral direction of the light from the biological substance S held on the holding surface 111 can be obtained. It is possible to prevent the light from being reflected to enter the semiconductor substrate 12, and as a result, it is possible to prevent color mixing between the pixels 11.
　膜１６は、図１２～図１４に示す第６実施形態～第８実施形態のように、前述したトレンチ１３Ｔ内にも含ませることができる。また、膜１６は、目的に応じて、複数の膜１６を積層させたり、図１４に示す第８実施形態のように、酸化膜１４と積層させることも可能である。 The film 16 can be included in the above-mentioned trench 13T as in the sixth to eighth embodiments shown in FIGS. 12 to 14. Further, the film 16 can be formed by laminating a plurality of films 16 or by laminating it with the oxide film 14 as in the eighth embodiment shown in FIG. 14, depending on the purpose.
　（５）第９実施形態～第１２実施形態
　図１５は、本技術に係る生体由来物質検出用チップ１の第９実施形態を模式的に示す模式断面図である。第９実施形態に係る生体由来物質検出用チップ１は、隣接する画素１１間の上方に設けられた遮光膜１７を備える。遮光膜１７を備えることで、画素１１間における混色を更に防止することができる。また、遮光膜１７を備えることで、保持表面１１１に液体サンプルを保持することができ、液体中に生体由来物質Ｓを保持することができる。 (5) Ninth Embodiment to Twelfth Embodiment FIG. 15 is a schematic cross-sectional view schematically showing a ninth embodiment of the biogenic substance detection chip 1 according to the present technology. The biogenic substance detection chip 1 according to the ninth embodiment includes the light shielding film 17 provided above the adjacent pixels 11. Providing the light-shielding film 17 can further prevent color mixing between the pixels 11. Further, by providing the light shielding film 17, the liquid sample can be held on the holding surface 111, and the biological substance S can be held in the liquid.
　遮光膜１７としては、遮光可能な素材で形成された膜であれば、膜を自由に選択することができる。例えば、タングステン（Ｗ）、アルミニウム（Ａｌ）、銅（Ｃｕ）、チタン（Ｔｉ）等の金属膜、光学黒色フィルター等が挙げられる。 The light-shielding film 17 can be freely selected as long as it is a film formed of a light-shielding material. For example, a metal film of tungsten (W), aluminum (Al), copper (Cu), titanium (Ti), etc., an optical black filter, etc. may be mentioned.
　遮光膜１７の形態は特に限定されず、目的に応じて自由に設計することができるが、図１６のＡ～Ｃに示すように、遮光膜１７間（即ち、保持表面１１１）が、上面視において、円形、楕円形、及び角がＲ形状の多角形から選択される１以上の形状を呈することが好ましい。このように、遮光膜１７間の上面視において、角を無くすことで、保持表面１１１へのサンプルの供給時の供給ムラや、保持表面１１１の洗浄時の洗浄不備等を防止することができる。その結果、検出精度の更なる向上を図ることができる。 The form of the light-shielding film 17 is not particularly limited and can be freely designed according to the purpose. However, as shown in FIGS. 16A to 16C, a portion between the light-shielding films 17 (that is, the holding surface 111) is viewed from above. In, it is preferable to exhibit one or more shapes selected from a circle, an ellipse, and a polygon having R-shaped corners. As described above, by eliminating the corners in the top view between the light shielding films 17, it is possible to prevent uneven supply when the sample is supplied to the holding surface 111, cleaning defects when cleaning the holding surface 111, and the like. As a result, the detection accuracy can be further improved.
　保持表面１１１へのサンプルの供給時の供給ムラや、保持表面１１１の洗浄時の洗浄不備等を防止する方法としては、その他の方法として、図１７に示す第１０実施形態のように、有機膜等を用いた平坦化膜１９を備える方法も採用可能である。 As a method for preventing the uneven supply during the supply of the sample to the holding surface 111 and the cleaning defect during the cleaning of the holding surface 111, as another method, as in the tenth embodiment shown in FIG. A method of providing the flattening film 19 using, for example, can also be adopted.
　遮光膜１７の下には、図１８に示す第１１実施形態のように、酸化膜１４のような他の膜を備えていても良い。また、遮光膜１７は、図１９に示す第１２実施形態のように、前述したトレンチ１３Ｔ内に埋め込んで、画素１１間の上方から半導体基板１２まで遮光壁を形成することも可能である。 Under the light shielding film 17, another film such as the oxide film 14 may be provided as in the eleventh embodiment shown in FIG. Further, as in the twelfth embodiment shown in FIG. 19, the light shielding film 17 can be embedded in the above-described trench 13T to form a light shielding wall from above the pixels 11 to the semiconductor substrate 12.
　なお、遮光膜１７は、図１５～図１９に示すように、画素１１毎に備えることもできるが、複数の画素１１単位で、遮光膜１７を設けることも可能である。 The light-shielding film 17 can be provided for each pixel 11 as shown in FIGS. 15 to 19, but it is also possible to provide the light-shielding film 17 for each of a plurality of pixels 11.
　（６）第１３実施形態、第１４実施形態
　図２０は、本技術に係る生体由来物質検出用チップ１の第１３実施形態を模式的に示す模式断面図である。第１３実施形態に係る生体由来物質検出用チップ１は、保持表面１１１が、半導体基板１２上に備えられたオンチップレンズ（ＯＣＬ）１８上に設けられている。オンチップレンズ（ＯＣＬ）を備えることで、生体由来物質Ｓからの光を、光電変換部１１２に集光することができ、各画素１１間における混色を更に防止することができる。 (6) Thirteenth Embodiment, Fourteenth Embodiment FIG. 20 is a schematic cross-sectional view schematically showing a thirteenth embodiment of the biogenic substance detection chip 1 according to the present technology. In the biogenic substance detection chip 1 according to the thirteenth embodiment, the holding surface 111 is provided on the on-chip lens (OCL) 18 provided on the semiconductor substrate 12. By providing the on-chip lens (OCL), the light from the biogenic substance S can be focused on the photoelectric conversion unit 112, and color mixing between the pixels 11 can be further prevented.
　オンチップレンズ（ＯＣＬ）１８の具体的な構成は特に限定されず、オンチップレンズ（ＯＣＬ）の構成（反射防止層等）を自由に選択して用いることができる。 The specific configuration of the on-chip lens (OCL) 18 is not particularly limited, and the configuration of the on-chip lens (OCL) (antireflection layer etc.) can be freely selected and used.
　オンチップレンズ（ＯＣＬ）１８には、図２１に示す第１４実施形態のように、平坦化膜１９を備えることができる。換言すると、保持表面１１１は、オンチップレンズ（ＯＣＬ）１８上に形成された平坦化膜１９上に設けることができる。平坦化膜１９を設けることで、保持表面１１１へのサンプルの供給時の供給ムラや、保持表面１１１の洗浄時の洗浄不備等を防止することができる。その結果、検出精度の更なる向上を図ることができる。 The on-chip lens (OCL) 18 can be provided with a flattening film 19 as in the fourteenth embodiment shown in FIG. In other words, the holding surface 111 can be provided on the flattening film 19 formed on the on-chip lens (OCL) 18. By providing the flattening film 19, it is possible to prevent uneven supply when the sample is supplied to the holding surface 111, cleaning defects when cleaning the holding surface 111, and the like. As a result, the detection accuracy can be further improved.
　なお、図２１に示す第１４実施形態では、遮光膜１７を平坦化するための平坦化膜１９ａと、オンチップレンズ（ＯＣＬ）を平坦化するための平坦化膜１９ｂとをそれぞれ備えているが、それぞれの平坦化膜１９ａと１９ｂとは、異なる材料で形成しても、同じ材料で形成してもよい。 The fourteenth embodiment shown in FIG. 21 includes a flattening film 19a for flattening the light shielding film 17 and a flattening film 19b for flattening the on-chip lens (OCL). The flattening films 19a and 19b may be made of different materials or the same material.
　（７）第１５実施形態
　図２２は、本技術に係る生体由来物質検出用チップ１の第１５実施形態を模式的に示す模式断面図である。第１５実施形態に係る生体由来物質検出用チップ１は、チップ表面に、保護膜２０を備える。保護膜２０を備えることで、熱、光、水、酸、アルカリ、又は薬剤等への対候性が向上し、水、酸、アルカリ、または薬剤に、長期間接触させることも可能となる。 (7) Fifteenth Embodiment FIG. 22 is a schematic cross-sectional view schematically showing a fifteenth embodiment of the biogenic substance detection chip 1 according to the present technology. The biogenic substance detection chip 1 according to the fifteenth embodiment includes a protective film 20 on the chip surface. The provision of the protective film 20 improves weather resistance to heat, light, water, acid, alkali, drug, etc., and allows contact with water, acid, alkali, or drug for a long period of time.
　保護層２０を形成する素材としては、熱、光、水、酸、アルカリ、又は薬剤等への対候性のある素材であれば、目的に応じて自由に選択して用いることができる。例えば、酸化シリコン（ＳｉＯ２）、窒化シリコン（Ｓｉ３Ｎ４）、シリコン酸窒化（ＳｉＯＮ）等を挙げることができる。 As a material for forming the protective layer 20, any material having weatherability against heat, light, water, acid, alkali, chemicals or the like can be freely selected and used according to the purpose. For example, silicon oxide (SiO 2 ), silicon nitride (Si 3 N 4 ), silicon oxynitride (SiON) and the like can be mentioned.
　（８）第１６実施形態
　図２３は、本技術に係る生体由来物質検出用チップ１の第１６実施形態を模式的に示す模式断面図である。第１６実施形態に係る生体由来物質検出用チップ１は、チップ表面に、励起光カットフィルタ２１を備える。励起光カットフィルタ２１を備えることで、励起光の光電変換部１１２への漏れ込みを防止することができる。その結果、検出精度の更なる向上を図ることができる。 (8) Sixteenth Embodiment FIG. 23 is a schematic cross-sectional view schematically showing a sixteenth embodiment of the biogenic substance detection chip 1 according to the present technology. The biogenic substance detection chip 1 according to the sixteenth embodiment includes an excitation light cut filter 21 on the chip surface. By including the excitation light cut filter 21, it is possible to prevent the excitation light from leaking into the photoelectric conversion unit 112. As a result, the detection accuracy can be further improved.
　（９）第１７実施形態
　図２４は、本技術に係る生体由来物質検出用チップ１の第１７実施形態を模式的に示す上方視模式平面図であり、図２５は、内部構造を省略した図２４のＡ－Ａ視断面模式図である。第１７実施形態に係る生体由来物質検出用チップ１は、有効画素領域１１Ｅの外側Ｏに段差部２２ａを備える。より詳細には、第１７実施形態に係る生体由来物質検出用チップ１は、有効画素領域１１Ｅから外側に向かって、中間領域２２、配線領域２３、周辺領域２４が設けられ、前記中間領域２２に、段差部２２ａを備える。有効画素領域１１Ｅの外側Ｏに備えられる配線領域２３には、段差があるのが一般的であるが、第１７実施形態では、配線領域２３と有効画素領域１１Ｅとの間の中間領域２２に段差部２２ａを設けることで、保持表面１１１へのサンプルの供給時の供給ムラや、保持表面１１１の洗浄時の洗浄不備等を防止することができる。その結果、検出精度の更なる向上を図ることができる。 (9) Seventeenth Embodiment FIG. 24 is a schematic plan view from above showing a seventeenth embodiment of the biogenic substance detection chip 1 according to the present technology, and FIG. 25 is a diagram with an internal structure omitted. FIG. 24 is a schematic cross-sectional view taken along line AA of 24. The biogenic substance detection chip 1 according to the seventeenth embodiment includes a step portion 22a on the outer side O of the effective pixel region 11E. More specifically, in the biogenic substance detection chip 1 according to the seventeenth embodiment, an intermediate region 22, a wiring region 23, and a peripheral region 24 are provided outward from the effective pixel region 11E, and the intermediate region 22 is provided. , A step 22a. The wiring region 23 provided on the outside O of the effective pixel region 11E generally has a step, but in the seventeenth embodiment, a step is formed in the intermediate region 22 between the wiring region 23 and the effective pixel region 11E. By providing the portion 22a, it is possible to prevent supply unevenness when the sample is supplied to the holding surface 111, cleaning defects when cleaning the holding surface 111, and the like. As a result, the detection accuracy can be further improved.
　図２４に示す通り、第７実施形態では、上面視において、段差部２２ａの角をＲ状に形成している。上面視において、段差部２２ａの角をＲ状に形成することで、保持表面１１１へのサンプルの供給時の供給ムラや、保持表面１１１の洗浄時の洗浄不備等を更に防止することができる。なお、図示しないが、上面視において、配線領域２３の角をＲ状に形成することも可能である。また、図示しないが、周辺領域２４に、段差部を設けることも可能である。 As shown in FIG. 24, in the seventh embodiment, the corners of the step portion 22a are formed in an R shape in a top view. By forming the corners of the step portion 22a into an R shape in a top view, it is possible to further prevent supply unevenness when the sample is supplied to the holding surface 111, cleaning defects when cleaning the holding surface 111, and the like. Although not shown, it is also possible to form the corners of the wiring region 23 in an R shape in a top view. Although not shown, a stepped portion can be provided in the peripheral region 24.
　なお、図示しないが、配線領域２３を、チップ１の保持表面１１１（受光面）とは反対側の表面側に設けることで、保持表面１１１へのサンプルの供給時の供給ムラや、保持表面１１１の洗浄時の洗浄不備等を防止することも可能である。 Although not shown, the wiring region 23 is provided on the surface side of the chip 1 opposite to the holding surface 111 (light receiving surface), so that the unevenness of supply when the sample is supplied to the holding surface 111 and the holding surface 111. It is also possible to prevent cleaning defects and the like during cleaning.
＜３．生体由来物質検出装置２＞
　図２６は、本技術に係る生体由来物質検出装置２の概念を示すブロック図である。本技術に係る生体由来物質検出装置２は、前述した本技術に係る生体由来物質検出用チップ１と、解析部２１と、を少なくとも備える。また、目的に応じて、光照射部２２、記憶部２３、表示部２４、温度制御部２５等を備えることもできる。以下、各部について説明する。なお、生体由来物質検出用チップ１については、前述の通りであるため、ここでは説明を割愛する。 <3. Biological substance detection device 2>
FIG. 26 is a block diagram showing the concept of the biological material detection device 2 according to the present technology. The biological substance detection device 2 according to the present technology includes at least the biological substance detection chip 1 according to the present technology described above, and the analysis unit 21. Further, the light irradiation unit 22, the storage unit 23, the display unit 24, the temperature control unit 25, and the like may be provided according to the purpose. Hereinafter, each part will be described. Since the biological substance detection chip 1 is as described above, the description thereof is omitted here.
　（１）解析部２１
　解析部２１では、生体由来物質検出用チップ１によって取得された電気的情報の解析が行われる。例えば、生体由来物質検出用チップ１によって取得された電気的情報に基づいて、生体由来物質Ｓの存在の有無、生体由来物質Ｓにおける相互作用の有無、薬効成分のスクリーニング等が行われる。 (1) Analysis unit 21
The analysis unit 21 analyzes the electrical information acquired by the biogenic substance detection chip 1. For example, based on the electrical information acquired by the biogenic substance detection chip 1, presence/absence of the biogenic substance S, presence/absence of interaction in the biogenic substance S, screening of a medicinal component, and the like are performed.
　なお、解析部２１としては、パーソナルコンピュータや、ＣＰＵにて実施してもよく、記録媒体（例えば、不揮発性メモリ（ＵＳＢメモリ）、ＨＤＤ、ＣＤなど）等を備えるハードウェア資源にプログラムとして格納し、パーソナルコンピュータやＣＰＵによって機能させることも可能である。 The analysis unit 21 may be implemented by a personal computer or a CPU, and is stored as a program in a hardware resource including a recording medium (for example, non-volatile memory (USB memory), HDD, CD, etc.). It is also possible to make it function by a personal computer or a CPU.
　（２）光照射部２２
　本技術に係る生体由来物質検出装置２には、例えば、励起光照射等のために光照射部２２を備えることができる。光照射部２２では、前記生体由来物質検出用チップ１の保持表面１１１に保持された生体由来物質Ｓへの光の照射が行われる。なお、本技術に係る生体由来物質検出装置２において、光照射部２２は必須ではなく、外部の光照射装置等を用いて生体由来物質Ｓへの光照射を行うことも可能である。 (2) Light irradiation unit 22
The living body-derived substance detection device 2 according to the present technology can be provided with a light irradiation unit 22 for, for example, excitation light irradiation. The light irradiation unit 22 irradiates the biological substance S held on the holding surface 111 of the biological substance detection chip 1 with light. In the living body-derived substance detection device 2 according to the present technology, the light irradiation unit 22 is not essential, and the living body-derived substance S can be irradiated with light using an external light irradiation device or the like.
　光照射部２２から照射される光の種類は特に限定されないが、微小粒子から蛍光や散乱光を確実に発生させるためには、光方向、波長、光強度が一定の光が望ましい。一例としては、レーザー、ＬＥＤ等を挙げることができる。レーザーを用いる場合、その種類も特に限定されないが、アルゴンイオン（Ar）レーザー、ヘリウム－ネオン（He-Ne）レーザー、ダイ（dye）レーザー、クリプトン（Cr）レーザー、半導体レーザー、または、半導体レーザーと波長変換光学素子を組み合わせた固体レーザー等を、１種又は２種以上、自由に組み合わせて用いることができる。 The type of light emitted from the light irradiation unit 22 is not particularly limited, but in order to reliably generate fluorescence or scattered light from fine particles, it is desirable that the light has a constant light direction, wavelength, and light intensity. A laser, LED, etc. can be mentioned as an example. When a laser is used, the kind is not particularly limited, but an argon ion (Ar) laser, a helium-neon (He-Ne) laser, a die (dye) laser, a krypton (Cr) laser, a semiconductor laser, or a semiconductor laser is used. One type or two or more types of solid-state lasers or the like combined with wavelength conversion optical elements can be freely combined and used.
　光照射部２２は、目的に応じて、複数備えてもよい。例えば、前記生体由来物質検出用チップ１の各画素１１に対して、一つの光照射部２２を備えてもよい。また、前記生体由来物質検出用チップ１の各画素１１に対応する位置にＬＥＤ等の発光素子が配列された基板を、前記生体由来物質検出用チップ１に積層させることで、生体由来物質Ｓへの光の照射を行うことも可能である。 A plurality of light irradiation units 22 may be provided according to the purpose. For example, one light irradiation unit 22 may be provided for each pixel 11 of the biogenic substance detection chip 1. In addition, by stacking a substrate on which light-emitting elements such as LEDs are arranged at positions corresponding to the respective pixels 11 of the biogenic substance detection chip 1 on the biogenic substance detection chip 1, the biogenic substance S is obtained. It is also possible to irradiate this light.
　（３）記憶部２３
　本技術に係る生体由来物質検出装置２には、各種情報を記憶する記憶部２３を備えることができる。記憶部２３には、前記生体由来物質検出用チップ１によって取得された電気的データ、解析部２１にて生成された解析データ、光照射部２２において照射した光学的データ等、検出に関わるあらゆる事項を記憶することが可能である。 (3) Storage unit 23
The living body-derived substance detection device 2 according to the present technology may include a storage unit 23 that stores various types of information. In the storage unit 23, all items related to detection, such as electrical data acquired by the biogenic substance detection chip 1, analysis data generated by the analysis unit 21, optical data irradiated by the light irradiation unit 22, and the like. It is possible to store
　本技術に係る生体由来物質検出装置２において、記憶部２３は必須ではなく、外部の記憶装置を接続してもよい。記憶部２３としては、例えば、ハードディスクなどを用いることができる。 In the biological substance detection device 2 according to the present technology, the storage unit 23 is not essential, and an external storage device may be connected. As the storage unit 23, for example, a hard disk or the like can be used.
　（４）表示部２４
　本技術に係る生体由来物質検出装置２には、各種情報を表示する表示部２４を備えることができる。表示部２４では、前記生体由来物質検出用チップ１によって取得された電気的データ、解析部２１にて生成された解析データ、光照射部２２において照射した光学的データ、記憶部２３に記憶されたデータ等、検出に関わるあらゆる事項を表示することができる。 (4) Display unit 24
The living body-derived substance detection device 2 according to the present technology can include a display unit 24 that displays various types of information. In the display unit 24, the electrical data acquired by the biogenic substance detection chip 1, the analysis data generated by the analysis unit 21, the optical data irradiated by the light irradiation unit 22, and the storage unit 23 are stored. All items related to detection such as data can be displayed.
　本技術に係る生体由来物質検出装置２において、表示部２４は必須ではなく、外部の表示装置を接続してもよい。表示部２４としては、例えば、ディスプレイやプリンタなどを用いることができる。 In the biological substance detection device 2 according to the present technology, the display unit 24 is not essential, and an external display device may be connected. As the display unit 24, for example, a display or a printer can be used.
　（５）温度制御部２５
　本技術に係る生体由来物質検出装置２には、生体由来物質検出用チップ１の保持表面１１１に保持された生体由来物質Ｓを所定の温度に保ったり、所定の温度に加熱又は冷却するための温度制御部２５を備えることができる。例えば、生体由来物質Ｓが酵素の場合、温度制御部２５よって、至適温度に保つように温度制御を行うことができる。また、生体由来物質Ｓが核酸であって、本技術を用いてハイブリダイゼーションの有無を検出する場合等には、ハイブリダイゼーション可能な温度範囲に保つように、温度制御部２５によって制御することができる。温度制御部２５としては、ペルチェ素子等の熱電素子を使用することができる。 (5) Temperature control unit 25
The biogenic substance detection device 2 according to the present technology is for holding the biogenic substance S held on the holding surface 111 of the biogenic substance detection chip 1 at a predetermined temperature, or for heating or cooling to a predetermined temperature. A temperature controller 25 can be provided. For example, when the biological substance S is an enzyme, the temperature control unit 25 can perform temperature control so as to maintain the optimum temperature. When the biogenic substance S is a nucleic acid and the presence or absence of hybridization is detected using the present technique, the temperature control unit 25 can control the temperature so that the temperature range can be hybridized. .. As the temperature control unit 25, a thermoelectric element such as a Peltier element can be used.
　温度制御部２５は、目的に応じて、複数備えてもよい。例えば、前記生体由来物質検出用チップ１の各画素１１に対して、一つの温度制御部２５を備えてもよい。また、前記生体由来物質検出用チップ１の各画素１１に対応する位置に熱電素子が配列された基板を、前記生体由来物質検出用チップ１に積層させることで、生体由来物質Ｓへの温度制御を行うことも可能である。 A plurality of temperature control units 25 may be provided according to the purpose. For example, one temperature control unit 25 may be provided for each pixel 11 of the biogenic substance detection chip 1. Further, by stacking a substrate on which thermoelectric elements are arranged at positions corresponding to the respective pixels 11 of the biogenic substance detection chip 1 on the biogenic substance detection chip 1, temperature control of the biogenic substance S is performed. It is also possible to do.
　なお、本技術に係る生体由来物質検出装置２において、温度制御部２５は必須ではなく、外部の温度制御装置等を用いて生体由来物質Ｓの温度制御を行うことも可能である。 Note that the temperature control unit 25 is not essential in the biological substance detection device 2 according to the present technology, and the temperature of the biological substance S can be controlled using an external temperature control device or the like.
＜４．生体由来物質検出システム３＞
　図２７は、本技術に係る生体由来物質検出システム３の概念を示すブロック図である。本技術に係る生体由来物質検出システム３は、前述した本技術に係る生体由来物質検出用チップ１と、解析装置３１と、を少なくとも備える。また、目的に応じて、光照射装置３２、記憶装置３３、表示装置３４、温度制御装置３５等を備えることもできる。 <4. Biological substance detection system 3>
FIG. 27 is a block diagram showing the concept of the biological material detection system 3 according to the present technology. The biogenic substance detection system 3 according to the present technology includes at least the biogenic substance detection chip 1 according to the present technology described above, and the analysis device 31. Further, the light irradiation device 32, the storage device 33, the display device 34, the temperature control device 35, and the like may be provided according to the purpose.
　生体由来物質検出用チップ１と、各装置とは、有線又は無線のネットワークを介して接続することが可能である。なお、各装置の詳細は、前述した本技術に生体由来物質検出装置２の各部の詳細と同一であるため、ここでは説明を割愛する。 The biogenic substance detection chip 1 and each device can be connected via a wired or wireless network. Since the details of each device are the same as the details of each part of the biological substance detection device 2 in the present technology described above, the description thereof is omitted here.
　なお、本技術では、以下の構成を取ることもできる。
（１）
　複数の画素から構成され、
　前記画素は、生体由来物質を保持する保持表面と、前記保持表面の下方に設けられ、半導体基板に設けられた光電変換部と、を少なくとも備え、
　前記画素間には混色抑制部が設けられた、生体由来物質検出用チップ。
（２）
　前記画素と前記混色抑制部とは異なる導電型である、（１）に記載の生体由来物質検出用チップ。
（３）
　前記画素はＮ型領域であり、前記混色抑制部はＰ型領域である、（２）に記載の生体由来物質検出用チップ。
（４）
　前記画素はＰ型領域であり、前記混色抑制部はＮ型領域である、（２）に記載の生体由来物質検出用チップ。
（５）
　前記複数の画素は、各々、光電変換領域を有し、各光電変換領域間にトレンチが設けられた、（１）から（４）のいずれかに記載の生体由来物質検出用チップ。
（６）
　前記トレンチの内部に、酸化膜、及び金属から選択される１種以上を含む、（５）に記載の生体由来物質検出用チップ。
（７）
　前記光電変換部の上方であって、前記保持表面に凹部が設けられている、（１）から（６）のいずれかに記載の生体由来物質検出用チップ。
（８）
　前記保持表面が、前記半導体基板上に形成された膜上に設けられた、（１）から（７）のいずれかに記載の生体由来物質検出用チップ。
（９）
　前記膜は第１の屈折率を有し、前記半導体基板は前記第１の屈折率とは異なる第２の屈折率を有する、（８）に記載の生体由来物質検出用チップ。
（１０）
　前記膜は、無機膜、及び有機膜から選択される１以上の膜からなる、（８）又は（９）に記載の生体由来物質検出用チップ。
（１１）
　隣接する前記画素間の上方に設けられた遮光膜を備える、（１）から（１０）のいずれかに記載の生体由来物質検出用チップ。
（１２）
　前記遮光膜間は、上面視において、円形、楕円形、及び角がＲ形状の多角形から選択される１以上の形状を呈する、（１１）に記載の生体由来物質検出用チップ。
（１３）
　前記保持表面が、前記半導体基板上に備えられたオンチップレンズ（ＯＣＬ）上に設けられた、（１）から（１２）のいずれかに記載の生体由来物質検出用チップ。
（１４）
　前記保持表面が、前記オンチップレンズ（ＯＣＬ）上に形成された平坦化膜上に設けられた、（１３）に記載の光検出用チップ。
（１５）
　前記生体由来物質は、核酸、タンパク質、細胞、微生物、染色体、リポソーム、ミトコンドリア、オルガネラ（細胞小器官）、及びこれらの複合体から選択される１以上の生体由来物質である、（１）から（１４）のいずれかに記載の光検出用チップ。
（１６）
　複数の画素から構成され、
前記画素は、生体由来物質を保持する保持表面と、前記保持表面の下方に設けられた光電変換部と、を少なくとも備え、
前記画素間には混色抑制部が設けられた、生体由来物質検出用チップと、
　前記生体由来物質検出用チップによって取得された電気的情報を解析する解析部と、
　を備える、生体由来物質検出装置。
（１７）
　複数の画素から構成され、
前記画素は、生体由来物質を保持する保持表面と、前記保持表面の下方に設けられた光電変換部と、を少なくとも備え、
前記画素間には混色抑制部が設けられた、生体由来物質検出用チップと、
　前記生体由来物質検出用チップによって取得された電気的情報を解析する解析装置と、
　を備える、生体由来物質検出システム。 Note that the present technology may also have the following configurations.
(1)
It consists of multiple pixels,
The pixel includes at least a holding surface that holds a biological substance, and a photoelectric conversion unit that is provided below the holding surface and that is provided on a semiconductor substrate.
A biogenic substance detection chip, in which a color mixture suppressing unit is provided between the pixels.
(2)
The biogenic substance detection chip according to (1), wherein the pixel and the color mixing suppression unit have different conductivity types.
(3)
The biogenic substance detection chip according to (2), wherein the pixel is an N-type region, and the color mixture suppressing portion is a P-type region.
(4)
The biogenic substance detection chip according to (2), wherein the pixel is a P-type region, and the color mixture suppressing portion is an N-type region.
(5)
The living body-derived substance detection chip according to any one of (1) to (4), wherein each of the plurality of pixels has a photoelectric conversion region, and a trench is provided between the photoelectric conversion regions.
(6)
The biogenic substance detection chip according to (5), wherein the inside of the trench contains at least one selected from an oxide film and a metal.
(7)
The biogenic substance detection chip according to any one of (1) to (6), wherein a recess is provided on the holding surface above the photoelectric conversion unit.
(8)
The biogenic substance detection chip according to any one of (1) to (7), wherein the holding surface is provided on a film formed on the semiconductor substrate.
(9)
The living body-derived substance detection chip according to (8), wherein the film has a first refractive index, and the semiconductor substrate has a second refractive index different from the first refractive index.
(10)
The biogenic substance detection chip according to (8) or (9), wherein the film is made of one or more films selected from an inorganic film and an organic film.
(11)
The biogenic substance detection chip according to any one of (1) to (10), comprising a light-shielding film provided above the adjacent pixels.
(12)
The chip for detecting a biological substance according to (11), wherein the space between the light shielding films has one or more shapes selected from a circle, an ellipse, and a polygon having an R shape in a top view.
(13)
The chip for detecting a biological substance according to any one of (1) to (12), wherein the holding surface is provided on an on-chip lens (OCL) provided on the semiconductor substrate.
(14)
The photodetection chip according to (13), wherein the holding surface is provided on a flattening film formed on the on-chip lens (OCL).
(15)
The biological substance is one or more biological substances selected from nucleic acids, proteins, cells, microorganisms, chromosomes, liposomes, mitochondria, organelles (organelles), and complexes thereof, (1) to ( The photodetection chip according to any one of 14).
(16)
It consists of multiple pixels,
The pixel includes at least a holding surface for holding a biological substance, and a photoelectric conversion unit provided below the holding surface,
A color mixing suppression part is provided between the pixels, a chip for detecting a biological substance,
An analysis unit that analyzes electrical information acquired by the biological substance detection chip,
An apparatus for detecting a substance derived from a living body, comprising:
(17)
It consists of multiple pixels,
The pixel includes at least a holding surface that holds a biological substance, and a photoelectric conversion unit provided below the holding surface,
A color mixture suppressing part is provided between the pixels, and a biological substance detection chip,
An analysis device for analyzing the electrical information acquired by the biogenic substance detection chip,
A biological substance detection system comprising:
１　生体由来物質検出用チップ
１１　画素
Ｓ　生体由来物質
１１１　保持表面
１２　半導体基板
１１２　光電変換部
１３　混色抑制部
１１２Ａ　光電変換領域
１３Ｔ　トレンチ
１４　酸化膜
１５　金属
１１１Ｃ　凹部
１６　膜
１７　遮光膜
１８　オンチップレンズ
１９　平坦化膜
２０　保護層
２１　励起光カットフィルタ
２２　中間領域
２３　配線領域
２４　周辺領域
２１　解析部
２２　光照射部
２３　記憶部
２４　表示部
２５　温度制御部
３１　解析装置
３２　光照射装置
３３　記憶装置
３４　表示装置
３５　温度制御装置 1 Biogenic Substance Detection Chip 11 Pixel S Biogenic Substance 111 Holding Surface 12 Semiconductor Substrate 112 Photoelectric Conversion Section 13 Color Mixing Suppression Section 112A Photoelectric Conversion Area 13T Trench 14 Oxide Film 15 Metal 111C Recess 16 Film 17 Light-Shielding Film 18 On-chip Lens 19 Flattening film 20 Protective layer 21 Excitation light cut filter 22 Intermediate area 23 Wiring area 24 Peripheral area 21 Analysis part 22 Light irradiation part 23 Storage part 24 Display part 25 Temperature control part 31 Analysis device 32 Light irradiation device 33 Storage device 34 Display device 35 Temperature control device

Claims (17)

  1. 　複数の画素から構成され、
    　前記画素は、生体由来物質を保持する保持表面と、前記保持表面の下方に設けられ、半導体基板に設けられた光電変換部と、を少なくとも備え、
    　前記画素間には混色抑制部が設けられた、生体由来物質検出用チップ。     It consists of multiple pixels,
    The pixel includes at least a holding surface that holds a biological substance, and a photoelectric conversion unit that is provided below the holding surface and that is provided on a semiconductor substrate.
    A biogenic substance detection chip, in which a color mixture suppressing unit is provided between the pixels.
  2. 　前記画素と前記混色抑制部とは異なる導電型である、請求項１記載の生体由来物質検出用チップ。 The biogenic substance detection chip according to claim 1, wherein the pixel and the color mixture suppressing unit have different conductivity types.
  3. 　前記画素はＮ型領域であり、前記混色抑制部はＰ型領域である、請求項２に記載の生体由来物質検出用チップ。 The biogenic substance detection chip according to claim 2, wherein the pixel is an N-type region, and the color mixture suppressing portion is a P-type region.
  4. 　前記画素はＰ型領域であり、前記混色抑制部はＮ型領域である、請求項２に記載の生体由来物質検出用チップ。 The biogenic substance detection chip according to claim 2, wherein the pixel is a P-type region and the color mixture suppressing portion is an N-type region.
  5. 　前記複数の画素は、各々、光電変換領域を有し、各光電変換領域間にトレンチが設けられた、請求項１記載の生体由来物質検出用チップ。 The biogenic substance detection chip according to claim 1, wherein each of the plurality of pixels has a photoelectric conversion region, and a trench is provided between the photoelectric conversion regions.
  6. 　前記トレンチの内部に、酸化膜、及び金属から選択される１種以上を含む、請求項５に記載の生体由来物質検出用チップ。 The chip for detecting a biological substance according to claim 5, wherein the trench contains at least one selected from an oxide film and a metal.
  7. 　前記光電変換部の上方であって、前記保持表面に凹部が設けられている、請求項１記載の生体由来物質検出用チップ。 The biogenic substance detection chip according to claim 1, wherein a recess is provided on the holding surface above the photoelectric conversion unit.
  8. 　前記保持表面が、前記半導体基板上に形成された膜上に設けられた、請求項１記載の生体由来物質検出用チップ。 The bio-derived substance detection chip according to claim 1, wherein the holding surface is provided on a film formed on the semiconductor substrate.
  9. 　前記膜は第１の屈折率を有し、前記半導体基板は前記第１の屈折率とは異なる第２の屈折率を有する、請求項８記載の生体由来物質検出用チップ。 The chip for detecting a biological substance according to claim 8, wherein the film has a first refractive index and the semiconductor substrate has a second refractive index different from the first refractive index.
  10. 　前記膜は、無機膜、及び有機膜から選択される１以上の膜からなる、請求項８記載の生体由来物質検出用チップ。 The chip for detecting a biological substance according to claim 8, wherein the film comprises one or more films selected from an inorganic film and an organic film.
  11. 　隣接する前記画素間の上方に設けられた遮光膜を備える、請求項１記載の生体由来物質検出用チップ。 The biogenic substance detection chip according to claim 1, further comprising a light-shielding film provided above the adjacent pixels.
  12. 　前記遮光膜間は、上面視において、円形、楕円形、及び角がＲ形状の多角形から選択される１以上の形状を呈する、請求項１１記載の生体由来物質検出用チップ。 The chip for detecting a biological substance according to claim 11, wherein a space between the light shielding films has one or more shapes selected from a circle, an ellipse, and a polygon having an R shape in a top view.
  13. 　前記保持表面が、前記半導体基板上に備えられたオンチップレンズ（ＯＣＬ）上に設けられた、請求項１記載の生体由来物質検出用チップ。 The biogenic substance detection chip according to claim 1, wherein the holding surface is provided on an on-chip lens (OCL) provided on the semiconductor substrate.
  14. 　前記保持表面が、前記オンチップレンズ（ＯＣＬ）上に形成された平坦化膜上に設けられた、請求項１３記載の光検出用チップ。 The photodetection chip according to claim 13, wherein the holding surface is provided on a flattening film formed on the on-chip lens (OCL).
  15. 　前記生体由来物質は、核酸、タンパク質、細胞、微生物、染色体、リポソーム、ミトコンドリア、オルガネラ（細胞小器官）、及びこれらの複合体から選択される１以上の生体由来物質である、請求項１記載の光検出用チップ。 The biological substance is one or more biological substances selected from nucleic acids, proteins, cells, microorganisms, chromosomes, liposomes, mitochondria, organelles (organelles), and complexes thereof. Light detection chip.
  16. 　複数の画素から構成され、
    前記画素は、生体由来物質を保持する保持表面と、前記保持表面の下方に設けられた光電変換部と、を少なくとも備え、
    前記画素間には混色抑制部が設けられた、生体由来物質検出用チップと、
    　前記生体由来物質検出用チップによって取得された電気的情報を解析する解析部と、
    　を備える、生体由来物質検出装置。     It consists of multiple pixels,
    The pixel includes at least a holding surface for holding a biological substance, and a photoelectric conversion unit provided below the holding surface,
    A color mixing suppression part is provided between the pixels, a chip for detecting a biological substance,
    An analysis unit that analyzes electrical information acquired by the biological substance detection chip,
    An apparatus for detecting a substance derived from a living body, comprising:
  17. 　複数の画素から構成され、
    前記画素は、生体由来物質を保持する保持表面と、前記保持表面の下方に設けられた光電変換部と、を少なくとも備え、
    前記画素間には混色抑制部が設けられた、生体由来物質検出用チップと、
    　前記生体由来物質検出用チップによって取得された電気的情報を解析する解析装置と、
    　を備える、生体由来物質検出システム。     It consists of multiple pixels,
    The pixel includes at least a holding surface for holding a biological substance, and a photoelectric conversion unit provided below the holding surface,
    A color mixing suppression part is provided between the pixels, a chip for detecting a biological substance,
    An analysis device that analyzes the electrical information acquired by the biogenic substance detection chip,
    A biological substance detection system comprising:
PCT/JP2019/043641 2018-11-26 2019-11-07 Chip for detecting material derived from living body, apparatus for detecting material derived from living body, and system for detecting material derived from living body WO2020110646A1 (en)

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